BACKGROUND:To investigate the value of pretreatment nasopharyngeal and neck magnetic resonance imaging (NN-MRI) combined with positron emission tomography (PET)/CT-guided therapy for improving survival in upper aerodigestive tract NK/T-cell lymphoma (UADT-NKTL) patients. METHODS:We performed a prospective cohort study including 171 untreated patients histologically diagnosed with UADT-NKTL, of whom 71 patients received PET/CT combined with NN-MRI and the other 100 patients received PET/CT alone. The clinical stage of every patient was classified according to the Ann Arbor and TNM staging systems. Clinical stage, target volume delineation, and survival were evaluated and compared for PET/CT with and without NN-MRI. RESULTS:By detecting additional local lesions, NN-MRI upgraded the clinical stages on the basis of the Ann Arbor staging system and TNM staging system compared to the results of PET/CT (9/71, p = 0.011; 11/71, p = 0.019, respectively), which revised the target volume delineation of radiotherapy (9/71) in the PET/CT-MRI group. Compared with those in the PET/CT group, 3-year local recurrence-free survival was prolonged in the PET/CT-MRI group (100% vs. 74.9%; p < 0.001), and 3-year overall survival and progression-free survival were better in the PET/CT-MRI group (84.5% vs. 76.3%, p = 0.04 and 78.3% vs. 67.3%, p = 0.03, respectively). CONCLUSION:NN-MRI and PET/CT-guided therapy could complementarily assist in optimizing the determination of clinical stage and target delineation, which could improve the prognosis of UADT-NKTL patients.

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.

BACKGROUND:The etiologic link between human papillomavirus (HPV) and lung cancer is still controversial.METHODS:PubMed and Cochrane databases were searched from inception to December 2020 to identify studies on the infection of HPV in lung cancer. We calculated the attributable proportion of HPV in lung cancer by pooling the infection of cases positive for both HPV DNA and biomarkers of carcinogenesis that may be induced by HPV (E6/E7 messenger RNA or p16INK4a).RESULTS:A total of 117 studies, comprising data of 12 616 lung cancer cases from 22 countries across 5 continents, were included. The overall HPV DNA positivity in primary lung cancer cases worldwide was 16.4% (95% confidence interval, 12.7%-20.5%). HPV DNA positivity of lung cancer varied significantly by pathological type and geographic region. Notably, the expression rate of p16INK4a is significantly higher than the positivity of HPV DNA and of HPV E6/E7 mRNA (P < .05). The estimate of HPV attributable proportion defined by expression of E6/E7 mRNA was 0 and of p16INK4a was 7.3%.CONCLUSIONS:The data in this systematic review is robust enough to contradict the possible participation of HPV in lung cancer carcinogenesis. Prophylactic vaccines targeting HPV cannot have the potential to prevent lung cancer.

BACKGROUND The etiologic link between HPV and lung cancer is still controversial. METHODS PubMed and Cochrane databases were searched from inception to December 2020 to identify studies on the infection of HPV in lung cancer. We calculated the attributable proportion of HPV in lung cancer by pooling the infection of cases positive for both HPV DNA and biomarker of carcinogenesis that may be induced by HPV (E6/E7 mRNA or p16INK4a). RESULTS A total of 117 studies, comprising data of 12,616 lung cancer cases from 22 countries across five continents, were included. The overall HPV DNA positivity in primary lung cancer cases worldwide was 16.4% (95% CI 12.7-20.5). HPV DNA positivity of lung cancer varied significantly by pathological type and geographic region. Notably, the expression rate of p16INK4a is significantly higher than the positivity of HPV DNA and of HPV E6/E7 mRNA (P < 0.05). The estimate of HPV attributable proportion defined by expression of E6/E7 mRNA was 0 and of p16INK4a was 7.3%. CONCLUSIONS The data in this systematic review is robust enough to contradict the possible participation of HPV in lung cancer carcinogenesis. Prophylactic vaccines targeting HPV cannot have the potential to prevent lung cancer.

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients with diffuse large B-cell lymphoma (DLBCL) in the elderly face challenges in treatment due to comorbidities and tolerance of chemotherapy. Besides, increased proportion of ABC/non-GCB subgroups, complex molecular features associated with unfavorable prognosis are also present with increased frequency with advancing age. These characteristics foreshadow distinct biological or immune microenvironment features of DLBCL in the elderly. Although clinical benefit of single-agent anti-PD-1 antibody in DLBCL was not obvious, pre-use anti-PD-1 antibody as first-line may be an opportune for elderly DLBCL. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody has been approved by the National Medical Products Administration for the treatment of various cancers. Aims: The primary endpoints were objective response rate (ORR) of rituximab combined with toripalimab and ORR after R-CHOP regimen. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. This trial was registered at ClinicalTrials.gov (NCT04058470). Methods: Patients aged 60-85 years, ECOG 0-2 with untreated DLBCL or grade 3b follicular lymphoma and at least one measurable or evaluable lesion were enrolled. This study consisted of a phase 1b (toripalimab dose escalation) followed by a phase 2 expansion portion. In the phase Ib, a standard “3 + 3” design was utilized to identify the MTD, DLT and recommended phase 2 dosage (RP2D) of toripalimab. In phase 2, patients received 2 cycles of toripalimab (RP2D) plus rituximab (375mg/m2) every 3 weeks. They allowed to accept two additional cycles of toripalimab plus rituximab (To-Ri) if they got complete response (CR) after the first 2 cycles. To-Ri followed by R-CHOP (21) up to 6 cycles then Toripalimab (RP2D) maintenance 6 cycles (q 30 days) after CR or CMR post R-CHOP. ORR based on Lugano 2016 criteria and adverse events (AEs) were defined according to CTCAE 5.0. Results: From December 2020 to February 2023, 48eligible patients were enrolled. Median age 67 years (range, 60-83), 20 (41.6%) male, 21 (43.8%) patients with stage III/IV, 34(70.8%) patients with extranodal disease, 12 (25.0%) patients with IPI score ≥ 3 points, and non-GCB(n=34), double expression (DEL, n=7), EBV+DLBCL(n=6), double/triple hit lymphoma (DHL/THL, n=2). In phase Ib, no MTD or DLT events were observed, RP2D of Toripalimab was 240mg. Of 44 response evaluable patients, 18 patients completed To-Ri×4, 33 (75.0%) achieved response including 22 (50.0%) patients with CR post To-Ri. Key responded to To-Ri including non-GCB (75.0%, n=24), GCB (57.1%, n=8), EBV+DLBCL (66.7%, n=4), DEL (85.7%, n=6), DHL/THL (100%, n=2), primary gastrointestinal tract involved (63.6%, n=7/11) and primary nasal involved (87.5%, 7/8). ORR and CR post R-CHOP were 100% (44/44) and 95.5% (42/44). With a median follow-up of 15.4 months, 1-year PFS and OS were 85.5% and 95.4%. Forty-four (100%) patients reported treatment-related AEs (TRAEs). The most frequently observed (≥10%) TRAEs were abnormal liver function (45.5%), anemia (43.2%), lymphopenia (34.1%), neutropenia (27.3%), hypothyroidism (22.7%), nausea (22.7%). Summary/Conclusion: Toripalimab plus Rituximab as a first-line treatment then followed by R-CHOP yielded high CR rate and manageable toxicities in newly diagnosed elderly DLBCL, especially for patients with extranodal disease and high-grade lymphoma. This treatment strategy deserves further study. Keywords: Phase II, DLBCL

Background: The role of adjuvant EGFR tyrosine kinase inhibitors (TKIs) in resected EGFR-mutated non-small-cell lung cancer (NSCLC) remains unclear. Materials & methods: We evaluated pooled hazard ratio and 95% CI for disease-free survival, overall survival and prespecified subgroups. Results: Seven prospective studies with 1288 patients were included in the meta-analysis. Adjuvant EGFR TKIs significantly improved disease-free survival in EGFR-mutated resected NSCLC (HR: 0.41; 95% CI: 0.24-0.70) and in all subgroups. However, the overall survival benefit was not significant (HR: 0.65; 95% CI: 0.36-1.17). The benefit of adjuvant TKIs may be associated with TKI regimens, treatment duration, pathological stage and EGFR mutation type. Conclusion: Adjuvant EGFR TKIs significantly improved disease-free survival and nonsignificantly improved overall survival in resected EGFR-mutated NSCLC.

Background: Patients with diffuse large B-cell lymphoma (DLBCL) in the elderly face challenges in treatment due to comorbidities and poor tolerance of chemotherapy. Age >60 years is an unfavorable risk factor in DLBCL in the International Prognostic Index (IPI) system. Besides, increased proportion of ABC/non-GCB subgroups, complex molecular features also lead to unfavorable prognosis with distinct biological or immune microenvironment features in elderly patients. Although clinical benefit of single-agent anti-PD-1 antibody in DLBCL was not obvious, pre-use anti-PD-1 antibody as first-line may be an opportune for elderly DLBCL. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody has been approved by the NMPA for the treatment of various cancers. Methods: Patients aged 60-85 years, ECOG 0-2 with untreated DLBCL or grade 3b follicular lymphoma and at least one measurable or evaluable lesion were enrolled. This study consisted of a phase 1b (Toripalimab dose escalation) followed by a Phase 2 expansion portion. In the phase Ib, a standard "3+3" design was utilized to identify the MTD, DLT and recommended phase 2 dosage (RP2D) of Toripalimab.In phase 2, patients received 2 cycles of Toripalimab (RP2D) plus Rituximab (375mg/m2) every 3 weeks. They allowed to accept two additional cycles of Toripalimab plus Rituximab (To-Ri) if they obtained complete response (CR) after the first 2 cycles. To-Ri followed by R-CHOP (21) up to 6 cycles without Toripalimab then Toripalimab (RP2D) maintenance 6 cycles (q 30 days) after CR or CMR post R-CHOP. All cases more than 75-year-old received R-miniCHOP. The primary endpoints were objective response rate (ORR) based on Lugano 2016 criteria and clinical benefit rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Adverse events (AEs) were defined according to CTCAE 5.0. This trial was registered at ClinicalTrials.gov (NCT04058470). Results: From December 2020 to July 2022, 37 eligible patients were enrolled. Median age 67 years (range, 60-83), 16 (43.2%) male, 20 (54.1%) patients with stage III/IV, 27(73.3%) patients with extranodal disease, 8 (21.6%) patients with IPI score ≥ 3 points, and non-GCB(n=25), double expression (DEL, n=7), EBV+DLBCL(n=5), double/triple hit lymphoma (DHL/THL, n=2). In phase Ib, no MTD or DLT events were observed, RP2D of Toripalimab was 240mg. Of 34 response evaluable patients, 14 patients completed To-Ri×4, 26 (59.1%) achieved response including 15 (44.1%) patients with CR post To-Ri treatment. Key responded to To-Ri including non-GCB (81.8%, n=18), GCB (58.3%, n=7), EBV+DLBCL (50%, n=2), DEL (87.5%, n=7), DHL/THL (100%, n=2), primary gastrointestinal tract involved (75%, 6/8) and primary nasal involved (87.5%, 7/8). Five patients are still under treatment, ORR and CR post R-CHOP were 100% (32/32) and 87.5% (28/32). With a median follow-up of 8.2 months, estimated 1-year PFS and were 81.2% and 88.4%. Thirty-six (97.3%) patients reported treatment-related AEs (TRAEs). The most frequently observed (≥10%) TRAEs were abnormal liver function (43.2%), anemia (43.2%), lymphopenia (32.4%), neutropenia (27.0%), hypothyroidism (21.6%), nausea (18.5%). This clinical trial is still on going. Conclusion: Toripalimab plus Rituximab as a first-line treatment then followed by R-CHOP yielded high CR rate and manageable toxicities in elderly with newly diagnosed DLBCL, especially for patients with extranodal disease and high grade lymphoma. This therapeutic strategy deserves further clinical investigation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract Background The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Methods Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression‐free survival (PFS)‐related nomogram. We also performed external validation of the nomogram in an independent cohort. Results We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C‐index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5‐year PFS was 98.9% for the low‐risk group and 69.3% for the high‐risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low‐risk group and 94.6% for the high‐risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5‐year PFS rates were 94.8% and 66.7% for the low‐risk and high‐risk groups, respectively (p < 0.001). The 5‐year OS rates were 97.9% and 88.4%, respectively (p = 0.016). Conclusion The nomogram could well distinguish the prognosis of low‐ and high‐risk patients with extragastric MALT lymphoma and is thus recommended for clinical use.

[This corrects the article DOI: 10.7150/thno.51245.].

Angioimmunoblastic T-cell lymphoma (AITL), a type of malignant lymphoma with unique genomic aberrations, significant clinicopathological features, and poor prognosis, is characterized by immune system dysregulation. Recent sequencing studies have identified recurrent mutations and interactions in tet methylcytosine dioxygenase 2 (TET2), ras homology family member A (RHOA), DNA methyltransferase 3 alpha (DNMT3A), and mitochondrial isocitrate dehydrogenase II (IDH2). Notably, since B-cell lymphomas are frequently observed along with AITL, this review first summarizes its controversial mechanisms based on traditional and recent views. Epigenetic regulation represented by TET2 plays an increasingly important role in understanding the multi-step and multi-lineage tumorigenesis of AITL, providing new research directions and treatment strategies for patients with AITL. Here, we review the latest advances in our understanding of AITL and highlight relevant issues that have yet to be addressed in clinical practice.

Thymic epithelial tumors (TETs) are one of the rarest adult malignancies in the anterior mediastinum. Thymic carcinomas (TCs) are less prevalent among TETs, but they are more clinically aggressive. Immunotherapy has emerged as a promising therapeutic approach for refractory TETs, even though chemotherapy remains the conventional treatment for the advanced disease. However, limited attention has been paid to the features of the tumor microenvironment (TME) which might provide clinically relevant information and guide treatment regimen design. Especially, to date, there have been only a few studies focusing on the differences between the TME and genomic features preserved by TETs and TCs. We analyzed the TME and genomic characteristics of TETs using RNA sequencing and whole-exome sequencing, finding that distinct characteristics of TME in different pathogenic subtypes of TETs. According to those findings, we found that thymic carcinomas had significantly lower expression of HMGB1, a pro-inflammatory cytokine-related gene, than thymomas, and low HMGB1 expression was linked to a poor prognosis. Additionally, higher mutation burdens were significantly associated with the later stage and more advanced pathological types. Thymoma patients with lower mutation burdens tended to relapse within 3 years. In summary, different characteristics of TME and genomic features between thymoma and thymic carcinoma were associated with clinical outcomes of TETs and presented promisingly predictive value for efficacy and toxicity of immunotherapy.

Purpose Primary thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of MALT lymphoma. We aim to investigate the clinicopathologic features, 18 F-FDG PET/CT findings and outcomes for patients with primary thymic MALT lymphoma; to explore the correlation between metabolic parameters and immunohistochemical phenotypes. Methods A retrospective single-center study enrolled 12 patients with primary thymic MALT lymphoma between 2010 and 2021. Nineteen 18 F-FDG PET/CT scans were performed, and clinicopathologic and immunohistochemical characteristics, PET/CT imaging features, and outcomes were analyzed. Results The male-to-female ratio was 1. The median age at diagnosis was 40 (range 31–68). The long diameter of the lesions ranged from 3.5 to 15.7. Histopathological examinations revealed that the normal thymic lobular architecture was effaced by a diffuse lymphoid infiltrate, but residual Hassall corpuscles could still be identified, mostly with CD20+, PAX5+, CD3-, CD23-, CD10-, BCL-6-, cyclin D1-, EBER- and low Ki-67. The gene rearrangement indicated that the IGH gene but not TCR gene was found in 7 patients. Six initial PET/CT scans showed a mean SUVmax of 6.8 (range, 3.1–12.4), a mean MTV = 40.0 (range, 6.7–81.4), and a mean TLG = 144.3 (range, 19.7–286.4). During the follow-up period, there was no death except for the patient with DLBCL who died 59 months after diagnosis of primary thymic MALT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.355, P > 0.05). Conclusion Primary thymic MALT lymphoma should be considered in patients with multilocular cystic lesions with different degrees of 18 F-FDG uptake in the anterior mediastinum. The results of this study showed no correlation between SUVmax and Ki-67 index.

BACKGROUND:Visceral pleural invasion (VPI) with PL1 or PL2 increases the T classification from T1 to T2 in non-small cell lung cancers (NSCLCs) ≤ 3 cm. We proposed a modified T classification based on VPI to guide adjuvant therapy. RESEARCH QUESTION:Is it reasonable to upstage PL1-positive cases from T1 to T2 for NSCLCs ≤ 3 cm? STUDY DESIGN AND METHODS:In total, 1,055 patients with resected NSCLC were retrospectively included. Tumor sections were restained with hematoxylin and eosin stain and Victoria blue elastic stain for the elastic layer. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Subgroup analysis and a Cox proportional hazards model were used to further determine the impact of VPI on survival. RESULTS:The extent of VPI was diagnosed as PL0 in 824 patients, PL1 in 133 patients, and PL2 in 98 patients. The 5-year DFS rates of patients with PL0, PL1, and PL2 were 62.6%, 60.2%, and 28.8% (P < .01), whereas the corresponding 5-year OS rates were 78.6%, 74.4%, and 50.0% (P < .01), respectively. As predicted, the DFS and OS of patients with PL2 were much worse than those of patients with PL0 (P < .01) and PL1 (P < .01). However, both the DFS and OS of patients with PL0 and PL1 were comparable (DFS: P = .198; OS: P = .150). For node-negative cases, the DFS and OS of patients with PL0 and PL1 were also comparable (DFS: P = .468; OS: P = .388), but patients with PL2 had much worse DFS and OS than patients with PL0 (P < .01) and PL1 (P < .01). Multivariable analyses suggested that PL2, together with node positivity and poor cell differentiation, was an independent adverse prognostic factor. INTERPRETATION:In NSCLCs ≤ 3 cm, tumors with PL1 should remain defined as T1, not T2. Overtreatment by adjuvant chemotherapy in node-negative NSCLCs ≤ 3 cm might be avoided in PL1 cases.

Background: Collagen type VI alpha 1 (COL6A1) has been found to be dysregulated in several human malignancies. However, the role of COL6A1 in osteosarcoma (OS) progression remains largely unclear. Here, we aimed to explore the clinical significance and biological involvement of COL6A1 in the OS cell migration and invasion. Material and Methods: We used immunohistochemistry, qRT-PCR and western blot to detect the expression of COL6A1 in 181 OS patient samples. Chromatin immunoprecipitation (ChIP) and PCR were carried out to verify the regulatory interaction of p300, c-Jun and COL6A1 promoter. The invasion and migration function of COL6A1 in OS was detected in vitro and in vivo. RNA sequence was performed to detect the downstream pathway of COL6A1, and then co-immunoprecipitation (co-IP), ubiquitination assays and rescue experiments were performed to determine the regulatory effect of COL6A1 and signal transducers and activators of transcription (STAT1). Exosomes derived from OS cell lines were assessed for the ability to promote cancer progression by co-cultured assay and exosomes tracing. Results: COL6A1 was commonly upregulated in OS tissues, especially in lung metastasis tissues, which was associated with a poor prognosis. c-Jun bound p300 increased the enrichment of H3K27ac at the promoter region of the COL6A1 gene, which resulted in the upregulation of COL6A1 in OS. Overexpression of COL6A1 promoted OS cell migration and invasion via interacting with SOCS5 to suppress STAT1 expression and activation in an ubiquitination and proteasomal degradation manner. Most interestingly, we found that exosomal COL6A1 derived from OS cells convert normal fibroblasts to cancer-associated fibroblasts (CAFs) by secreting pro-inflammatory cytokines, including IL-6 and IL-8. The activated CAFs could promote OS cell invasion and migration by mediating TGF-β/COL6A1 signaling pathway. Conclusion: Our data demonstrated that upregulation of COL6A1 activated by H3K27 acetylation promoted the cell migration and invasion by suppressing STAT1 pathway in OS cells. Moreover, COL6A1 can be packaged into OS cell-derived exosomes and activate CAFs to promote OS metastasis.

Immune transcripts are essential for depicting onco-immunologic interactions. However, whether cancer cells mimic immune transcripts to reprogram onco-immunologic interaction remains unclear. Here, single-cell transcriptomic analyses of 7,737 normal and 37,476 cancer cells reveal increased immune transcripts in cancer cells. Cells gradually acquire immune transcripts in malignant transformation. Notably, cancer cell-derived immune transcripts contribute to distinct prognoses of immune gene signatures. Optimized immune response signature (oIRS), obtained by excluding cancer-related immune genes from immune gene signatures, and offers a more reliable prognostic value. oIRS reveals that antigen presentation, NK cell killing and T cell signaling are associated with favorable prognosis. Patients with higher oIRS expression are associated with favorable responses to immunotherapy. Indeed, CD83+ cell infiltration, which indicates antigen presentation activity, predicts favorable prognosis in breast cancer. These findings unveil that immune mimicry is a distinct cancer hallmark, providing an example of cancer cell plasticity and a refined view of tumor microenvironment.

Background: Stage III follicular lymphoma (FL) is currently still considered incurable after RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy and rituximab maintenance. Radiotherapy plays a vital role in early-stage FL, but the value remains unclear in stage III FL. Here, we reported the results of invasive field radiotherapy (IFRT) combined with rituximab maintenance versus rituximab maintenance alone in patients with stage III FL who achieved complete remission (CR) or partial response (PR) after induction chemotherapy.

ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody in vitro and in vivo models in non-small cell lung carcinoma (NSCLC) cells. Mechanistically, PD0325901 or shRNA-ERK1/2 significantly downregulated the PD-L1 expression in NSCLC cells and increased the CD3+ T cells infiltration and functions in tumor tissue. There was a positive correlation between the p-ERK1/2 expression and PD-L1 expression in patients with NSCLC. And the patients with low p-ERK1/2 expression were observed a high response rate of PD-1/PD-L1 blockage therapy. Our results demonstrate that PD0325901, an ERK inhibitor, can enhance the efficacy of PD-1 blockage against NSCLC in vitro and in vivo models. And the combination of ERK inhibitor such as PD0325901 and PD-1/PD-L1 blockage is a promising regimen and encouraged to be further confirmed in the treatment of patients with NSCLC.

Abstract Background Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. Methods NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. Results Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). Conclusions Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.