Cholesterol metabolic reprogramming is an emerging vulnerability in cancer, yet clinical progress has been limited by a lack of druggable targets. Here, we identify the sterol-sensing domain (SSD) of SCAP as a target in gastric cancer (GC), with multi-omics confirming tumor-specific SCAP overexpression, poor prognosis, and hyperactivated synthesis. Using SSD structure-based high-throughput screening, we discovered that the natural compound Platycodin D (PD) is a small-molecule inhibitor of SCAP. PD sustains SREBP2 activation yet paradoxically blocks cholesterol efflux. The underlying mechanism is that PD specifically disrupts SCAP's sterol-sensing function, thereby permitting unrestrained SREBP2-mediated biosynthesis. This critical dysfunction leads to pathological cholesterol overload in the endoplasmic reticulum (ER), inducing proteotoxic stress. Consequently, this stress disrupts Nrf1 ER retention and forces nuclear translocation, thereby compromising LXR-mediated efflux. We further demonstrate that this SCAP targeting initiates GPX4 cascade-mediated ferroptosis, which was reversible by inhibiting cholesterol synthesis or the stress response. PD demonstrated potent tumor suppression with a significantly improved safety profile compared to cisplatin in vivo. Our work establishes a causal link between SSD disruption and ferroptotic death via cholesterol dysregulation, introducing a novel paradigm for exploiting metabolic vulnerabilities in GC therapy.

BACKGROUND:Colorectal cancer exhibits limited responsiveness to immune-checkpoint blockade, primarily because an elevated intratumoral Treg/CD8+ T-cell ratio extinguishes antitumor immunity. The molecular determinants that lock this immunosuppressive balance are unknown. METHODS:We integrated single-cell RNA-seq, TCGA WGCNA, and spatial transcriptomics to nominate candidate regulators of the Treg/CD8+ ratio. CRISPR-Cas9 was used to generate HSPB1-knockout MC38 and SW480 cell lines. Subcutaneous models were employed to assess tumor growth. Immune profiling was performed by multiparametric flow cytometry; mechanistic dissection combined bulk RNA-seq, Transwell assays, western blot and in vitro T-cell polarization systems. RESULTS:Single-cell profiling and TCGA WGCNA analyze identified HSPB1 as a putative determinant of the intratumoral Treg/CD8+ T-cell ratio, and survival analysis showed its prognostic relevance in CRC. Spatial transcriptomics revealed colocalization of HSPB1-expressing tumor cells with Tregs. Subcutaneous tumor models demonstrated that HSPB1 genetic deletion or pharmacological inhibition markedly suppressed tumor growth and abolish the Treg-dominated microenvironment. In vitro polarization assays confirmed that targeting HSPB1 selectively restrains Treg differentiation without affecting Th17. Integrated transcriptomic and functional assays further elucidated that HSPB1 orchestrates Treg recruitment via the CCL20-CCR6 axis, thereby shaping the immunosuppressive milieu within colorectal tumors. CONCLUSIONS:Targeting HSPB1 exerts dual anti-tumor effects: it directly suppresses neoplastic proliferation and simultaneously alleviates Treg-mediated immunosuppression within the tumor microenvironment.

BackgroundThe aim of this retrospective study was to investigate the efficacy and safety of different regimes among patients with intrahepatic cholangiocarcinoma (ICC).MethodsThe data of 232 patients (2011-2023) at the Tianjin Medical University Cancer Institute&Hospital were analyzed. Patients were divided into 5 different groups: non-AT group (underwent surgical treatment alone), gemcitabine plus oxaliplatin (GEMOX), gemcitabine plus immunotherapy, capecitabine monotherapy and capecitabine plus immunotherapy.ResultsSignificant differences were observed in both RFS (p = 0.045) and OS (p = 0.0084) between CH group (GEMOX and capecitabine) and non-AT group. No significant difference was observed in RFS (p = 0.73) or OS (p = 0.47) between capecitabine and GEMOX. However, GEMOX group had higher incidence of grade 3-4 adverse reactions(n=7, 17.1%). When comparing the CH and gemcitabine plus immunotherapy and capecitabine plus immunotherapy group, no significant differences were observed in RFS or OS. In subgroup analysis, patients with CA19-9>39 U/ml and ALP>100 U/L may benefited from chemotherapy combined with immunotherapy.ConclusionCompared to GEMOX, capecitabine showed no significant difference in prognosis but exhibited a more favorable safety profile. Although the addition of immunotherapy did not confer further benefit in the overall cohort, it was associated with improved efficacy in patients with CA19-9 >39 U/ml or ALP >100 U/L. These findings require confirmation in larger studies.

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression. However, the mechanisms underlying the posttranscriptional regulation of TAMs remain largely unknown. Here, we demonstrated that Trmt61a, the "writer" enzyme of tRNA N1-methyladenosine (m1A) modification, is highly expressed in proinflammatory macrophages in tumor microenvironment. We generated conditional knockout (KO) mice for Trmt61a and observed that Trmt61a deletion in macrophages significantly promoted tumor growth. Mechanistically, we identified that m1A maintains the translation of STING, enhances STING-TBK1-IFN-β signaling in macrophages and therefore suppresses tumor cell growth. We further generated TRMT61A-overexpressing human iPSC-derived CAR-macrophage and demonstrated that human TRMT61A effectively promoted antitumor CAR-macrophage therapy in vivo. Collectively, our findings reveal a novel regulatory mechanism of tRNA m1A modification in macrophages, highlighting the antitumor therapeutic potential of targeting tRNA m1A modification in macrophages.

Patients with newly diagnosed or relapsed/refractory (R/R) anaplastic thyroid cancer (ATC) and R/R poorly differentiated thyroid cancer (PDTC) have limited treatment options and an overall poor prognosis. ICAM-1, a cell surface glycoprotein also known as CD54 overexpressed in a variety of cancers including thyroid cancers, is known to play a key role in tumorigenesis. AIC100 is a 3rd generation ICAM-1 directed CAR T-cell product engineered with affinity-tuned technology to selectively bind and kill tumor cells to improve safety. Another unique feature for AIC100 is co-expression of somatostatin receptor 2 to allow CAR T-cell monitoring with DOTATATE PET scan. We present here updated results from phase 1 dose-escalation clinical trial NCT04420754. The multicenter study was designed to explore 3 dose levels (DLs) of AIC100 at 1x 107, 1 x 108, and 5 x 108, respectively. An additional DL4 (7.5 x 108) was explored since no dose-limiting toxicities (DLTs) were observed previously. Key eligibility included adult patients (≥18 years) with newly diagnosed or R/R ATC or R/R PDTC, who had measurable disease, and with ECOG status 0-2. AIC100 was infused intravenously 48 hours after completing lymphodepletion (Fludarabine/Cyclophosphamide x 3 days). Primary objectives included safety assessment/DLTs within 30 days of AIC100 infusion and to determine the recommended phase 2 dose (RP2D). As of 12-Dec-2024, 24 patients were enrolled and 15 (8 ATC; 7 PDTC) with a median age of 59 (range, 47-69) years were infused with AIC100 at 4 DLs. Patients were predominantly male (N = 11), with a median of 2 (range, 1-4) prior lines of systemic therapies. No DLTs were observed in the originally planned DLs 1-3. Two patients in the exploratory DL4 developed grade 3 pneumonitis. 10 (66.7%) patients developed grade 1/2 CRS. No ICANS or other SAEs related to AIC100 occurred at DLs 1-3. 11 patients were evaluable for efficacy in DLs 1-3 at day 42 after infusion; responses were assessed per study site. No responses were observed in DL1. For evaluable patients in DL 2 and 3 (n = 9), the objective response rate (ORR) and disease control rate (DCR, defined as ORR + stable disease (SD)) were 22% and 56%, respectively. For ATC patients at DL2-DL3 (N=4), the ORR was 50% [1 each with partial response (PR) and complete response (CR) in DL 2 and 3, respectively]. In PDTC at DL2-DL3 (N=5), DCR was 60%. AIC100 expansion was observed in all patients. Additional transaltional data will be presented at the meeting. Based on safety and efficacy, 5 x 108 (DL3) was declared as RP2D. AIC100, a first-in-human ICAM-1 directed CAR T-cell therapy, demonstrated an acceptable safety profile in patients with relapsed/refractory ATC and PDTCs. The observed durable responses in DL2 and DL3 are encouraging and provide a proof of concept for potential role of AIC100 in aggressive thyroid cancer patients and other advanced cancers. DL3 is determined as the RP2D. Cohort expansion at RP2D will be initiated in Q2 2025 in 2 indications; ATC and PDTC. Samer A. Srour, Jochen H. Lorch, Mark E. Zafereo, Victoria M. Villaflor, Yan Xing, Sonal Gupta, Mimi I-Nan Hu, Ramona Dadu, Adam Lin, Yang Lu, Melissa Cushing, Scott Avecilla, Theresa Scognamiglio, Moonsoo Jin, Janusz Puc, Tripti Gaur Gaur, Stacey Ukrainskyj, Sebastian A. Mayer, Koen Van Besien, Maria E. Cabanallas. ICAM-1 directed chimeric antigen receptor (CAR) T cells (AIC100) in patients with advanced thyroid cancers: Clinical and translational data from the phase 1 dose escalation study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT206.

Immunotherapy has emerged as a key modality in cancer treatment by activating the host immune system to recognize and eliminate tumor cells, demonstrating significant efficacy across various solid tumors. However, the complexity of the tumor microenvironment and the presence of immunosuppressive factors limit the effectiveness of immunotherapy when used alone. To overcome these limitations, combining immune checkpoint inhibitors (ICIs) with anti-angiogenic therapy has gained increasing attention. Mechanistic studies have shown that this combination can modulate the tumor microenvironment on multiple levels, enhancing antitumor immune responses and improving clinical outcomes. Clinical trials have further validated the efficacy and safety of this strategy in multiple solid tumor types, highlighting its promising clinical potential. Nonetheless, challenges such as treatment-related toxicity, lack of reliable biomarkers, and therapy resistance persist. This review systematically summarizes the mechanistic insights and current clinical progress of ICI-based combination therapy with anti-angiogenic agents, discusses existing challenges, and explores future directions to inform the optimization and precision of combined treatment approaches.

We conceived of a type of antitumor mechanism of action by which a soluble target in the tumor microenvironment, such as a tumor-driving growth factor, can be phagocytized along with cancer cells via antibody-dependent cellular phagocytosis (ADCP) using an antibody bispecific for the soluble target and a solid target overexpressed on the cancer cell surface. We explored this concept through engineering bispecific antibodies (BsAbs) co-targeting human epidermal growth factor receptor-2 (HER2) and vascular endothelial growth factor A (VEGFA) in an scFv-IgG format (VHS). We showed that the HER2-VEGFA BsAbs but not the parental antibodies alone or in combination induced co-phagocytosis of VEGFA and HER2-overexpressing cancer cells by tumor-associated macrophages via ADCP. In both immunocompromised and immunocompetent mice with aggressive tumors, the BsAbs demonstrated greater anti-metastasis activity and produced a greater survival benefit than the parental antibodies alone or in combination, in a manner dependent on Fcγ receptors on the macrophages. Our results provide proof of the concept that HER2-VEGFA BsAbs achieve enhanced antitumor activity by leveraging HER2 overexpressed on the cancer cell surface to induce co-phagocytosis of VEGFA. Our findings warrant clinical testing of the strategy to treat metastasis and recurrence of HER2-overexpressing solid tumors that respond to anti-VEGFA therapy.

ObjectivePorphyromonas gingivalis (P. gingivalis) infection is a recognized pathogenic factor in colorectal cancer (CRC), and extracellular vesicles (EVs) are key mediators within the tumor microenvironment. However, the molecular composition of large extracellular vesicles (lEVs) derived from P. gingivalis-infected cancer cells remains poorly characterized. This study aimed to comprehensively define the molecular cargo alterations in lEVs secreted by CRC cells in response to P. gingivalis infection.MethodsAn integrated multiomics approach was employed to analyze lEVs secreted by P. gingivalis-infected HCT116 colorectal cancer cells. miRNA sequencing and quantitative proteomics were used to profile miRNA and protein expression, respectively. Bioinformatic analyses identified differentially expressed molecules. Mechanistic studies involving immunoblotting and autophagy inhibition were conducted to validate and explore key findings.ResultsP. gingivalis infection induced significant cargo remodeling in HCT116-derived lEVs. miRNA sequencing identified 223 miRNAs, among which 28 were differentially expressed. Notably, six novel miRNAs were specifically upregulated in lEVs from infected cells. Quantitative proteomics revealed 1,210 significantly altered proteins. Strikingly, 981 proteins were downregulated, including the critical antitumor immune regulator STING (stimulator of interferon genes). STING downregulation in infected HCT116 cells was confirmed, and P. gingivalis infection was shown to promote STING degradation via autophagy, explaining its reduced incorporation into lEVs.ConclusionThis integrated multiomics analysis demonstrates that P. gingivalis infection profoundly remodels the molecular landscape of CRC cell-derived lEVs. The specific depletion of immune-stimulating factors, most notably STING, within lEVs suggests a novel mechanism by which this pathobiont may contribute to immune evasion and promote tumor progression in P. gingivalis-associated colorectal cancer.

A substantial proportion of patients with intrahepatic cholangiocarcinoma (ICC) present with symptoms such as fever or abdominal pain, which are frequently linked to unfavorable prognostic outcomes. A retrospective analysis of the clinical data from 125 patients diagnosed with ICC was conducted. Univariate and multivariate analyses were carried out to assess overall survival (OS) and disease-free survival (DFS). Subsequently, the patients were stratified into 2 groups based on the presence or absence of symptoms. The presence of symptoms is recognized as a risk factor associated with an unfavorable prognosis (OS: 2.026 [1.133–3.624], P = .017); DFS: 1.590 [1.004–2.517], P = .048). Patients presenting symptoms exhibit a higher prevalence of lymph node metastasis ( P = .032), microvascular invasion ( P = .041), and higher CA19-9 levels ( P = .020). Survival curves revealed that OS ( P = .010) and DFS ( P = .017) were significantly poorer among patients with ICC exhibiting COX-2 (+). Moreover, an analysis of the immune microenvironment in patients with COX-2 (+) indicated a higher presence of CD163+ cells ( P = .018) compared to that of patients with COX-2 (−). ICC patients with symptoms are associated with a dismal prognosis and a pronounced expression of COX-2 within the tumor tissues. Our study suggests that preoperative symptoms may serve as a clinical indicator of aggressive tumor biology and immune microenvironment alterations, and that COX-2 expression may represent a potential therapeutic target.

Objectives: Immune-mediated colitis (IMC) is a common immune-related adverse event during immune checkpoint inhibitor (ICI) therapy. This case series and review aimed to highlight atypical cases of IMC and explore the potential of PET/CT to predict imminent ICI colitis. Methods: Through a descriptive, retrospective study at a tertiary cancer center, we identified adult patients receiving ICIs for any cancer between 2010 and 2022 who also underwent PET/CT for routine cancer surveillance during this time. We included patients who had signs and symptoms of colitis and reviewed their surveillance PET/CT scans obtained 2 to 6 weeks before and up to 3 months after diagnosis. Results: For the 33 included patients, surveillance scans were reviewed in collaboration with a nuclear radiologist. A total of 17 patients (51.5%) received combination therapy, while 14 (42.4%) received anti–PD-1/PD-L1 monotherapy. While ICI therapy has a median duration of 6.5 months, most patients (72.7%) had negative surveillance PET/CT for colitis. Diarrhea and colitis severity were similar among those with positive and negative findings for colitis on surveillance PET/CT. The outcomes of colitis were similar, with an 81.8% resolution in patients with negative PET/CT and 71.4% in patients with positive PET/CT. Conclusions: PET/CT imaging did not appear to assist in predicting IMC. This may be due to the long interval between clinical IMC and surveillance PET/CT imaging. The continued use of clinical criteria combined with laboratory markers, e.g., lactoferrin and calprotectin, and endoscopy/histology will enable more accurate detection and timely treatment of IMC.

ObjectiveThis study aims to elucidate the distribution patterns of immune cells associated with the programmed cell death protein 1 (PD-1) pathway within esophageal cancer (EC) tissues and to determine their correlation with patient prognosis.MethodsWe included tissue samples from 236 EC patients who had undergone surgery at our institution between January 2016 and January 2021. This study examined the correlation between six immunohistochemical markers and the clinical profiles of these patients. Survival analysis was performed using the Kaplan-Meier method and the LOG-rank test to evaluate the impact of immunohistochemical marker expression on patient survival. A clinical predictive model was developed and validated for prognostic assessment.ResultsExpression levels of PD-1, PD-L1, FOXP3, and CD25 were found to be positively associated with the depth of tumor invasion and lymph node metastasis (P < 0.05). In contrast, CD4 and CD8 expression levels were inversely related to these parameters (P < 0.05). High expression of PD-1, PD-L1, FOXP3, and CD25, along with lymph node metastasis, were identified as independent prognostic risk factors (P < 0.05). Patients with low expression of PD-1, PD-L1, FOXP3, CD25, and high expression of CD4 and CD8 exhibited improved three-year survival rates (P < 0.001). The predictive model, based on these factors, demonstrated high discrimination and accuracy.ConclusionA prognostic model incorporating the expression levels of PD-1, PD-L1, FOXP3, CD25, and lymphocyte infiltration offers robust predictive validity for the prognosis of EC patients.

Olfactory neuroblastoma (ONB) is a rare malignancy known to originate from the olfactory epithelium. The complex tumor ecosystem of this pathology remains unclear. Here we explored the cellular components within 10 ONB tumors and 1 olfactory mucosa sample based on single cell RNA profiles. We showed the intra-tumoral heterogeneity by identifying five unique expression programs among malignant epithelial cells. A novel three-classification system (Neural/Basal/Mesenchymal) of ONB was established according to the distinguished gene expression patterns. Biomarkers for categorizing bulk tumors into the new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be cautiously inferred according to the molecular features representing three tumor types,thus helping with precision chemotherapy. Herein, we also analyzed subclusters of tumor microenvironment (TME) and the interactions among different cell types in the TME. Relative abundance of immunosuppressive tumor associated macrophages indicated the benefits of immunotherapies targeting macrophages.

BackgroundMetastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs.MethodsThe Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0–2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting.FindingsFrom March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18–49). The overall response rate was 25·0% (95% CI 7·3–52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study.InterpretationCabozantinib shows promising activity in patients with MPPGs.FundingTeam NAT Foundation, Margaret Cazalot, and Clarence P Cazalot.

Purpose Exposure to immune checkpoint inhibitors (ICIs) can predispose to immune-related adverse events (irAEs) involving the gastrointestinal tract. The association between ICIs and bowel perforation has not been well studied. We aimed to describe the clinical course, complications, treatment, and outcomes of patients experiencing bowel perforation during or after ICI treatment.Methods This retrospective, single-center study included adult cancer patients with bowel perforation that occurred between the first dose of ICI treatment and up to 1 year thereafter between 1/1/2010 and 4/30/2021. Patients' clinical course, imaging, treatment, and outcomes related to bowel perforation were collected and analyzed.Results Of the 13,991 patients who received ICIs during the study period, 90 (0.6%) met the inclusion criteria. A majority were male (54.4%), the most common cancer type was melanoma (23.3%), and most patients had received PD-1/L1 inhibitor treatment (58.8%). Onset of perforation occurred after a median of four ICI treatment cycles. The most common symptom was abdominal pain (95.5%). The colon was the most common location for the perforation (37.7%). Evidence of diverticulitis, enterocolitis, or appendicitis was seen in 32 (35.6%) patients, and 6 (6.6%) patients had luminal cancer involvement at the time of perforation. The overall hospitalization rate related to perforation was 95.5%, with mortality of 15.5% during the same admission. Antibiotics were given in 95% of our sample; 37.8% of patients also required surgical/interventional radiology intervention. Forty-six patients (51.1%) had perforation-related complications (e.g., sepsis, fistula, abscess), which were associated with a higher mortality rate (30%).Conclusion Our findings suggest a low incidence of bowel perforation after ICI treatment (0.6%), with 40% of patients having coexisting bowel inflammation as a potential contributing factor. Patients with bowel perforation had an aggressive disease course and high rates of hospitalization, complications, and mortality. Early recognition and prompt intervention is critical to improve patient outcomes. Future studies are warranted to further investigate the cause, predictive markers, and optimal treatment for this patient population.

Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3–4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.

Table S1: Cell lines used in the current study

Introduction: Metformin is a commonly used treatment for diabetes mellitus that has been shown to increase F-18 fluorodeoxyglucose (FDG) uptake in the gastrointestinal (GI) system, which could have a similar imaging presentation as enterocolitis on positron emission tomography/computed tomography (PET/CT) scan. This mimicking feature could lead to confusion of subclinical enterocolitis and impact clinical management, especially in patients on immune checkpoint inhibitors (ICI) as enterocolitis is one of the common adverse events related to ICI. We are interested to study the incidence and characteristics of patients with diagnosis of clinical enterocolitis among patients on metformin and ICI who had PET/CT evidence of FDG uptake in GI tract. Methods: We conducted a retrospective single-center study among cancer patients concurrently receiving metformin and ICI (01/01/2010-09/30/2022) who underwent a PET/CT scan during their treatment. Cases with reported suspicious positive PET/CT signal for GI tract were extracted and analyzed for colitis incidence, clinical and imaging presentations. Results: Among 1869 PET scans in 1259 patients in the study window, 361 patients had positive enterocolitis reported on 535 PET/CT scan tests. After manual chart review, 157 patients were included as the final cohort with the following demographics: median age 67 (58-73), male gender (69.4%), cancer type (lung, head & neck in 36.9%, melanoma in 24.8%, gastrointestinal in 8.9%, genitourinary in 6.4%), and ICI treatment (anti-PD-1/L1 monotherapy in 80.8%, combination of CTLA-4 and PD-1/L1 in 19.2%). Total 70 of 157 patients had a clinical diagnosis of ICI enterocolitis (44.6%). The features of positive FDG uptake on PET/CT appeared comparable between patients with clinical enterocolitis and those without which could be due to the metformin effect (Figure 1). No specific characteristics such as standardized uptake value (SUV) level have been observed to differentiate the metformin effect vs immune related enterocolitis. Conclusion: The signal of FDG uptake is comparable between the metformin effect and ICI enterocolitis on PET/CT. The FDG positivity does not necessarily associate with ICI enterocolitis. The management is still relying on the standard clinical and endoscopy evaluation for final confirmation.Figure 1.: Captions are present in the image already.

Immune checkpoint inhibitor (ICI) therapy may give rise to immune-related adverse events (irAEs). Pneumatosis intestinalis (PI), or gas within the bowel wall, has very rarely been observed following ICI therapy, and its clinical significance is unclear. We described the clinical characteristics and outcomes of PI as a possible irAE in cancer patients. We retrospectively identified 12 adult cancer patients with radiologic evidence of PI within 1 year after ICI exposure during January 2010–January 2023. Clinical characteristics, treatment, and outcomes were evaluated. The median age of our sample was 64 years. The most common cancer types were thoracic/head neck and gastrointestinal. Eleven patients (92