Therapeutic options remain limited for advanced intracranial malignancies, including brain metastases and glioblastomas, particularly in patients ineligible for surgery, radiotherapy, or systemic therapies. This phase 1 study evaluates the safety and feasibility of intracranial administration of low-dose pemetrexed followed by RetroNectin-activated killer cells (RAKs) and interleukin 2 via an Ommaya reservoir (collectively referred to as SCOPE-T) in 25 patients with refractory intracranial malignancies. Nineteen patients completed at least one treatment cycle, and 17 received the maximum tested RAK dose (5 × 108 cells). Treatment is well tolerated, with no treatment-related adverse events greater than grade 2; transient fever and headache are the most common toxicities. Exploratory radiographic and clinical assessments suggest disease stabilization in evaluable patients. These findings support the feasibility and safety of intracranial SCOPE-T and indicate preliminary signals of therapeutic activity. Given the small sample size and non-randomized design, the results should be interpreted as exploratory (ClinicalTrials.gov: NCT05459441).

The concurrent presence of COVID-19 infection in advanced cancer patients has increased the mortality since the compromised immunity was inevitably worsen. The role and clinical impact of autologous adoptive T cell immunotherapy (ACT) designed for anti-cancer treatment were not known in such circumstances. The safety and potential immune reconstitution of concurrent ACT in advanced cancer patients with active COVID-19 infection have yet unknown as well. The effect of infused ACT on the symptom severity manifestation should be summarized. In this respectively clinical observation study, patients were non-randomized enrolled from the two centers according to the regular therapeutic plans including stage IV cancer patients for scheduled ACT, chemotherapy, cancer patients with symptomatic COVID-19 but without ACT, neither cancer or non-ACT but symptomatic cases of COVID-19 infection. We have incorporated the age-adjusted Charlson comorbidity index (aCCI) for each patient to compare the prognosis of the three groups. All patients were planned for the scheduled standard anti-cancer therapeutic considerations, chemotherapy plus ACT as planned as well as the supportive care.The clinical efficacy and impact of ACT on cancer patients within the 3 months from the peripheral blood apheresis, dendritic cell (DC) and cytokine induced killer T cell (CIK-T ) infusion and subsequent co-existence of COVID-19 infection were recorded as the primary objective. During the same period, the cancer cases without ACT and others were collected to compare the occurrence of both severe and death rate respectively. There were 123 patients (35 of ACT, 23 of non-ACT, 65 of non-cancer) with similar aCCI. There were similar cohort-level COVID-19 in-hospital case fatality rates consistent with previously reported data for non-cancer (26.2

IntroductionImmune thrombocytopenia (ITP) is the most common bleeding disorder in children. Tfh cells play a crucial role in the pathogenesis of ITP by promoting the production of anti-platelet autoantibodies. Recent studies have shown that CXCR5+γδ T cells not only possess “Tfh-like” cell functions but also can induce Tfh cell differentiation. However, it remains unknown whether CXCR5+γδ T cells are involved in the pathogenesis of ITP. This study aims to investigate the role of CXCR5+γδ T cells in children with newly diagnosed ITP (nITP).MethodsA total of 96 children with nITP and 48 healthy children were enrolled in this study. FCM was used to compare the frequencies of circulating CXCR5+γδ T cells and circulating Tfh cells, as well as the levels of ICOS and CD40l on circulating CXCR5+γδ T cells in both groups. The correlation between circulating CXCR5+γδ T cells and platelets as well as circulating Tfh cells were further analyzed.ResultsCompared with healthy controls, the frequency of circulating CXCR5+γδ T cells was higher in children with nITP, and it was negatively correlated with platelet count. The levels of ICOS and CD40l on circulating CXCR5+γδ T cells in children with nITP were also higher. Children with nITP had a higher frequency of circulating Tfh cells, which was positively correlated with circulating CXCR5+γδ T cells.ConclusionsThe excessive activation and proliferation of CXCR5+γδ T cells may contribute to the pathogenesis of nITP in children. Therefore, it can be used as a target for the immunotherapy of pediatric ITP.

Immune checkpoint inhibitor PD-1 antibody (PD-1-Ab) has arisen the increasing clinical prevalence of immune-related adverse events (irAEs) such as hypothyroidism. Hypothyroidism is the common irAEs, but the mechanism of such immunological pathogenesis was still unclear. We have developed a unique hypothyroidism mice model induced by mimicking clinical exposure to PD-1-Ab. Then we analyzed the immune cell phenotypes in the peripheral blood of mouse models by flow cytometry and further verified in patients' samples. Therefore, we have further investigated the molecular pathogenesis of such condition through the spatial transcriptome sequencing in thyroid glands. Those findings have supported the recommendations of prophylactic treatment with thyroxine in a very beginning timepoint. The results showed that the CD4+T-cell subset declined in the peripheral blood of hypothyroidism mice induced by PD-1-Ab, which was consistent with the similarities in the patients with hypothyroidism. Moreover, spatial transcriptome sequencing of thyroid glands of mice was predominantly featured by upregulated IL-17 signaling pathway and involved endoplasmic reticulum stress, which provided the evidences to address the preliminary roles of immunological pathogenesis participated. In addition, we have demonstrated that a combination with early onset of thyroxine supplements could prevent the subsequent occurrence of hypothyroidism. Those experimental and clinical data provided the awareness that CD4+T cells are associated with hypothyroidism caused by PD-1-Ab, and therefore, prophylactic administration of thyroxine should be considered with great caution and in timely manner.NEW & NOTEWORTHY This study explored the immunopathogenic mechanism of immune checkpoint inhibitor associated hypothyroidism through T-cell phenotype and spatial transcriptome sequencing of thyroid glands of mimicked mice model. The findings revealed decreased CD4+T-cell subset and subsequently featured by upregulated IL-17 signaling pathway. The prophylactic thyroxine was recommended in the early onset of hypothyroidism.

Purpose Immune checkpoint inhibitors (ICIs) and target therapy have provided the clinical efficacy for improving the clinical progression-free survival (PFS) and overall survival (OS) for patients with renal cell carcinoma (RCC). There has been little report of an surrogate salvage treatment for those failure of both ICIs and target. An innovation therapeutic model named SHAPE-T (synchronized hyperthermia with ex vivo autologous progenitor expanded T cells) was applied to previously heavily treated metastatic RCC (mRCC). The safety and clinical response with a three-year follow-up were filed.Materials and methods This was N-of-1 clinical study describing such mRCC case with ECOG 3-4 score was treated by SHAPE-T. The peripheral blood apheresis was completed to produce ACT in vitro periodically .The nonimplantable in-depth hyperthermia device where the intratumor temperature could reach 42.5 C was performed for the average of 45 min, twice per week. One cycle ACT constituted three infusions of RetroNectin activated killer (RAK)cells at each 28 days interval. One SHAPE-T therapeutic schema included two cycles of 42.6 billion of RAKs plus 10 times of hyperthermia. The primary endpoints were PFS and OS. The clinical safety and efficacy of treatment cycles of infused T cells and therapeutic cycle were recorded.Results The enrolled patient was successfully recovered to complete response with OS exceeded 40 months. The ECOG performance recovered and sustained to score 0. There were less adverse reactions associated with SHAPE-T.Conclusions The intractable and progressive mRCC could be salvaged by SHAPE-T. This was the first case that provide the insights into the importance of the SHAPE-T.

Backgroud: The tumor immune microenvironment influences the efficiency of concurrent chemoradiotherapy (CCRT) in high-grade glioma (HGG). This study investigated peripheral blood T lymphocyte subsets as clinical indicators of therapeutic response and prognosis in pediatric high-grade glioma (pHGG). Methods: This retrospective study included 77 patients with postoperative pHGG who were treated concurrently with temozolomide and external beam radiotherapy between January 1, 2012, and December 31, 2018. The median follow-up was 26 (range: 5-106) months. Peripheral venous blood samples were collected before and after CCRT. The proportions of peripheral blood T lymphocytes and their association with treatment outcome and survival were determined. Results: Sixty-four (83.1%) patients achieved complete remission, partial remission, and stable disease, and 13 (16.9%) patients had progressive disease. Higher CD3 + T cell, CD4 + T cell, and CD8 + CD28 + T cell ratios were predictive of better response, while a higher CD8 + CD28 − T cell ratio was predictive of poorer response. Binary logistic regression analysis showed that the CD8 + CD28 + T cell ratio was a significant independent predictor of CCRT response (odds ratio [OR] = 53.521, 95% confidence interval [CI] = 4.294-667.119, P = .002). Univariate and multivariate analysis of prognostic factors associated with survival showed that the CD8 + CD28 + T lymphocyte ratio was a significant independent predictor of progression-free survival (hazard ratio [HR] = 1.80, 95% CI = 1.06-3.08, P = .03), but none of the subsets were significantly associated with overall survival. Conclusion: Peripheral blood T lymphocytes have potential as predictors of CCRT response and prognosis in pHGG. Keywords High-grade glioma , concurrent chemoradiotherapy , lymphocyte subsets , flow cytometry , prognosis

Backgroud: The tumor immune microenvironment influences the efficiency of concurrent chemoradiotherapy (CCRT) in high-grade glioma (HGG). This study investigated peripheral blood T lymphocyte subsets as clinical indicators of therapeutic response and prognosis in pediatric high-grade glioma (pHGG). Methods: This retrospective study included 77 patients with postoperative pHGG who were treated concurrently with temozolomide and external beam radiotherapy between January 1, 2012, and December 31, 2018. The median follow-up was 26 (range: 5-106) months. Peripheral venous blood samples were collected before and after CCRT. The proportions of peripheral blood T lymphocytes and their association with treatment outcome and survival were determined. Results: Sixty-four (83.1%) patients achieved complete remission, partial remission, and stable disease, and 13 (16.9%) patients had progressive disease. Higher CD3 + T cell, CD4 + T cell, and CD8 + CD28 + T cell ratios were predictive of better response, while a higher CD8 + CD28 − T cell ratio was predictive of poorer response. Binary logistic regression analysis showed that the CD8 + CD28 + T cell ratio was a significant independent predictor of CCRT response (odds ratio [OR] = 53.521, 95% confidence interval [CI] = 4.294-667.119, P = .002). Univariate and multivariate analysis of prognostic factors associated with survival showed that the CD8 + CD28 + T lymphocyte ratio was a significant independent predictor of progression-free survival (hazard ratio [HR] = 1.80, 95% CI = 1.06-3.08, P = .03), but none of the subsets were significantly associated with overall survival. Conclusion: Peripheral blood T lymphocytes have potential as predictors of CCRT response and prognosis in pHGG.

Background: Patients with malignant tumors are at a higher risk of severe infection and death from SARS-CoV-2 (COVID-19) than the general population, so finding ways to protect patients with malignant tumor infected COVID-19 are critical.Methods: In this cohort study using evidence based clincal outcome among participants were previously treated, stage IV cancer patients admitted to the hospital for scheduled adoptive cellular immune-therapeutic (ACT) during the COVID-19 outbreak infection in Shanghai from November 2022 to February 2023 with a diagnosis of COVID-19 infection. The matched corhort of COVID-19 infected cancer patients in Beijing, without treated with ACT during the same time period, were served as a control group. A third group included non-cancer patients admitted with COVID-19 infection. COVID-19 in-hospital case mortality rate and symptomatic severity occurrence, defined as the number of deaths and symptomatic severity that occurred during the surging period were calculated for each group. The age-adjusted Charlson Comorbidity Index (ACCI), determined for each patient, was used to compare the prognosis of the three groups.Findings: There were 123 patients (35 of ACT, 23 of non-ACT, 65 of non-cancer) who were admitted to the hospital from November 1 to December 31, 2022, with a diagnosis of COVID-19. The three groups had similar ACCI[1], The cohort-level COVID-19 in-hospital case fatality rates were 0% (0/35), 52.2% (12/23) and 26.2% (17/65) for the ACT, non-ACT, and non-cancer groups respectively. The frequency of severe cases was 11.4%, 100%, and 73.8% for the ACT, non-ACT, and non-cancer groups, respectively. Patients receiving ACT had a shorter mean time to alleviation of symptoms (4.46 versus 16.88 and17.90 days respectively) and had a lower severity incidence of symptoms (P=0.0010) . CD3-CD16+CD56+ NK cells increased following the ACT compared with the other patient subgroups (P = 0.0017) of cancer patients. ACT significantly decreased the substantial case fatality rate among cancer patients with COVID-19 during the outbreak. The time to symptom alleviation was significantly shorter in cancer patients treated with ACT than other patients. These data suggest a potential prophylactic role of ACT as an effective therapeutic alternative for suppressing COVID-related immunodeficiency and complications.Interpretation: In this cohort study of 123 patients, included those receiving ACT, those not receiving ACT, and non-cancer patients, who were hospitalizaed with COVID-19 from November 1 to December 31, 2022, ACT was associated with lower mortality and symptomatic severity and expedited symptom alleviation. The results of this study suggest that immune restoration through ACT may rescue cancer patients with immunodeficiency from chemotherapy who are at risk of COVID-19-related mortalit.Funding: This work has been supported by Shanghai Pudong New Area Health Commission Discipline Construction Project-Clinical Plateau Discipline (PWYgy2021-01) ; Shanghai Pudong New Area Health Commission Discipline Construction Project -Key Subject Group (PWZxq2022-14); Pudong New Area Clinical Characteristic Discipline Project (PWYts2021-11).Declaration of Interest: No potential conflicts of interest were disclosed.Ethical Approval: This study was approved by the Medical Ethics Committee of Fudan University Pudong Medical Center,Shanghai, China. Written informed consent to participate in this study was obtained from all patients at the time of admission.

<p>Supplementary table 3: Hematological and nonhaematologic adverse events.</p>

<p>Supplementary table 1: Cox proportional hazard regression analysis of patients' demographic and clinical characteristics related with overall survival.</p>

Copy number variants (CNVs) in plasma samples

Abstract Background: The renal clear cell carcinoma (RCCC) is a frequent occurrence of kidney cancer, such tumor was concealed progressed until symptomatic developed or through imaging examination. More recently, targeted therapies, immunotherapy and their combinations have improved outcome .However seeking the novel salvage treatment of second-line or above of post-immunotherapy has been warranted.Case presentation: A 55-year-old man diagnosed with non-VHL associated renal clear cell carcinoma presented 8 years ago. The upper abdominal distention and hematochezia were noticed after 6 years of nephrectomy, surgically confirmed pancreas-duodenal metastatic lesions 1.5 years ago to preclude the second primary carcinoma. Despite eight cycles of pembrolizumab plus axitinib after surgery, liver multiple masses progress rapidly. Following four cycles of autologous adoptive T cell immunotherapy and hyperthermia with low dose pembrolizumab, all metastatic lesions demonstrated complete responses. No serious adverse events were reported.Conclusions: This triple combination of adoptive T cell therapy, low dose immune checkpoint blockade, and hyperthermia has been salvage treatment for RCCC.

Human microbiota influence the response of malignancies to treatment with immune checkpoint blockade; however, their impact on other forms of immunotherapy is poorly understood. This study explored the effect of blood microbiota on clinical efficacy, represented by progression-free survival (PFS) and overall survival (OS), of combined chemotherapy and adoptive cellular therapy (ACT) in advanced colon cancer patients. Plasma was collected from colorectal cancer patients (CRC) treated with either chemotherapy alone (oxaliplatin and capecitabine) (XELOX CT alone group, n = 19), or ACT with a mixed dendritic cell/cytokine-induced killer cell product (DC-CIK) + XELOX (ICT group, n = 20). Circulating microbiota analysis was performed by PCR amplification and next-generation sequencing of variable regions V3~V4 of bacterial 16S rRNA genes. The association of the blood microbial diversity with clinical response to the therapy as measured by RECIST1.1 and OS was evaluated. The baseline Chao index of blood microbial diversity predicted prolonged PFS and OS of DC/CIK immunotherapy. More diverse blood microbiota that included Bifidobacterium, Lactobacillus, and Enterococcus were identified among responders to DC/CIK compared with non-responders. The plasma bacterial DNA copy number is inversely correlated with the CD3−/CD16+/CD56+ NK cells in circulation and decreased following DC-CIK; however, the Chao index of plasma microbiota significantly increased after administration of the DC-CIK product and this subsequent change was correlated with the number of CD3−/CD16+/CD56+ and CD8+/CD28+ cells infused. The diversity of the blood microbiome is a promising predictive marker for clinical responses to chemotherapy combined with DC-CIK. Cellular immunotherapy can affect the plasma microbiota’s diversity in a manner favorable to clinical responses.

Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC), frequent despite the availability of multiple treatment modalities, may be partly explained by the presence of immunosuppressive cell populations. We hypothesized that progression of disease could be prevented by the administration of an activated T cell immunotherapy (ACT) at time points when immunosuppressive populations increased in peripheral blood. In an N-of-1 study, a patient with multiple primary bladder high grade urothelial carcinomas, previously treated with standard local resection and chemotherapy but with evidence of progression, received ACT consisting of dendritic cells mixed with cytokine induced killer cells (DC/CIK), intravenously 18 times over a 6 year period at indicated time of observed increases in peripheral blood immunosuppressive CD8+/CD28- cells. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Cystoscopy and pelvic CT scans were performed at routine intervals to assess clinical status of disease. There has been no recurrence or metastasis of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions evidenced by the two more proof-of concept cases. ctDNA analysis detected mutations in six genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) which appeared at different times, but all of them disappeared after the DC-CIK infusions. These data suggest that DC/CIK infusions may be associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival.

PURPOSE:Radiation therapy (RT) modulates immune cells and cytokines, resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during RT for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described.METHODS AND MATERIALS:The study population consisted of children (n = 83, aged 3~18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors (GCT), and central nervous system embryonal tumor-not otherwise specified), with or without residual or disseminated (R/D) diseases who were starting standard postoperative focal or craniospinal irradiation (CSI). Peripheral blood T lymphocyte subsets collected before and 4 weeks after RT were enumerated by flow cytometry. Plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, and IL-17A were measured by cytometric bead array.RESULTS:Patients with R/D lesions receiving CSI (n = 32) had a post-RT increase in the frequency of CD3+T and CD8+T cells, a decrease in CD4+T cells, and an increase in regulatory T cells (Tregs) and CD8+CD28- suppressor cells, which was more predominantly seen in these patients than in other groups. In the CSI group with such R/D lesions, consisting of patients with medulloblastoma and germ cell tumors, 19 experienced a complete response (CR) and 13 experienced a partial response (PR) on imaging at 4 weeks after RT. The post/pre-RT ratio of Tregs (P = .0493), IL-6 (P = .0111), and IL-10 (P = .0070) was lower in the CR group than in the PR group. Multivariate analysis revealed that the post/pre-RT ratios of Treg, IL-6, and IL-10 were independent predictors of CR (P < .0001, P = .018, P < .0001, respectively). The areas under the receiver operating curves and confidence intervals were 0.7652 (0.5831-0.8964), 0.7794 (0.5980-0.9067), and 0.7085 (0.5223-0.8552) for IL-6, IL-10, and Treg, respectively. The sensitivities of IL-6, IL-10, and Treg to predict radiotherapeutic responses were 100%, 92.3%, and 61.5%, and specificity was 52.6%, 57.9%, and 84.2%, respectively.CONCLUSIONS:CSI treatment to those with R/D lesions predominantly exerted an effect on antitumor immune response compared with both R/D lesion-free but exposed to focal or CSI RT and with R/D lesions and exposed to focal RT. Such CSI with R/D lesions group experiencing CR is more likely to have a decrease in immunoinhibitory molecules and cells than patients who only achieve PR. Measuring peripheral blood Treg, IL-6, and IL-10 levels could be valuable for predicting radiotherapeutic responses of pediatric brain tumors with R/D lesions to CSI for medulloblastoma and intracranial germ cell tumors.

Background: Sepsis is considered to be a systemic in�ammatory response due to infection, resulting in organ dysfunction. Timely targeted interventions can reduce mortality and improve prognosis. Therefore, it is important to identify potential sepsis in time. In�ammation plays a crucial role in the process of sepsis. We combined in�ammatory markers to develop and validate a nomogram model and a simple risk scoring model for predicting sepsis in critically ill patients. Furthermore, comparing the prediction performance of the two models. Methods: The medical records of adult patients admitted to our intensive care unit (ICU) from August 2017 to December 2020 were analyzed. The �nally included patients were randomly divided into training cohort (70%) and validation cohort (30%). A nomogram model for sepsis was developed through multivariate logistic regression analysis in the training cohort. The continuous variables included in nomogram model were transformed into dichotomous variables. Then a multivariable logistic regression analysis was performed based on these dichotomous variables and the odds ratio (OR) for each variable was used to construct a simple risk scoring model for predicting sepsis. The receiver operating characteristic curves (ROC) were constructed and the area under the curve (AUC) was calculated to evaluate the discrimination performance of the two models. Results: According to our inclusion and exclusion criteria, 2074 patients were included in study. Finally, white blood cell (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR) were included in our models. The AUC of the nomogram model was 0.854 (95%CI: 0.835-0.872). The AUC of the simple risk scoring model was 0.842 (95%CI: 0.822-0.861). When the cut-off value was 7.5 points, the sensitivity was 77.03% and the speci�city was 75.75%. The prediction performance of the two models on sepsis is comparable (p=0.1298) and better than that of Sequential Organ Failure Assessment (SOFA) scores (AUC=0.759). Conclusions: This study combining �ve commonly available in�ammatory markers (WBC, CRP, IL-6, PCT and NLR) developed a nomogram model and a simple risk scoring model to predict sepsis in critically ill patients. Although the prediction performance of the two models is comparable, the simple risk scoring model may be simpler and more practical for clinicians to identify potential sepsis in critically ill patients at an early stage and make treatment strategies. cell, CRP C-reactive protein, neutrophil-to-lymphocyte ratio, OR odds ratio, CI con�dence area under the curve; BMI:body mass index; CRP:C-reactive protein; CIs:con�dence intervals; HR:heart rate; ICU:intensive care unit; IL-6:interleukin-6; NLR:neutrophil-to-lymphocyte ratio; OR:odds ratio; PCT:procalcitonin; RR:respiratory rate; ROC:receiver operating characteristic curves; SOFA:Sequential Organ Failure Assessment; SBP:systolic blood pressure; SIRS:systemic in�ammatory response syndrome; WBC:white blood cell.

Abstract Background Our understanding of sepsis-associated immune impairment is incomplete. The objective of this retrospective study was to investigate correlations of sepsis clinical manifestations with peripheral blood lymphocyte subpopulations in lymphocyte immunity. Methods Twenty individuals without sepsis and eighteen with sepsis were enrolled. Lymphocyte phenotypes (CD3+, CD4+, CD8+, CD3-CD16+CD56+, CD19+, CD4+CD25+CD127+, CD8+CD28-, and CD8+CD28+) were assessed by flow cytometry. Fresh fecal bacteria cue proportion was measured to determine intestinal dysbacteriosis. Results Compared with the non-sepsis group, the sepsis patients had clearly lower proportions of CD3+, CD4+ and CD8+CD28+ cells and substantially higher proportions of CD19+ cells (p<0.05). Among 38 patients with infection, CD4+ cells and CD8+CD28+ cells in a survivor group had significantly higher presence compared with patients who had died (p<0.05), The subgroup analysis results showed that CD4+ cells in the survivor subgroups were higher than those in the deceased subgroups (p<0.05). CD8+CD28+ cells in the non-sepsis survivor subgroup were higher than those in the deceased subgroups (p<0.05).. Bivariate correlation analysis showed that the intestinal dysbacteriosis was significantly correlated with the severity of sepsis and its prognosis (r2=0.2788, p=0.001, r2=0.1764, p=0.009, respectively). CD4+, CD19+, and CD8+CD28+ cells were significantly correlated with intestinal dysbacteriosis (r2=0.1024, p=0.049, r2=0.1063, p=0.046, r2=0.1909, p=0.006, respectively). Conclusions In conclusion, the lymphocyte populations of CD3+, CD4+, CD8+CD28+ and CD19+ cells were accessible for predicting the severity and mortality of sepsis patients. In addition, intestinal dysbacteriosis had a significant impact on the immune system of sepsis patients as revealed by peripheral blood lymphocyte population.

Introduction: Immunotherapy is now a standard treatment for many malignancies. Although immune checkpoint inhibition has demonstrated substantial efficacy by enhancing T cell activation and function in the tumor microenvironment, adoptive transfer of T and NK cell products promises to provide activated cells capable of immediate and direct tumor destruction. A widely applicable, non-MHC dependent, cellular therapy, consisting of in vitro generated dendritic cells (DC) combined with cytokine-induced killer cells (CIK), is highly efficient to produce from individual patients and has demonstrated safety and efficacy alone or with chemotherapy.Areas covered: We summarize the clinical data from studies of DC-CIK and discuss future research directions.Expert opinion: Patients with a wide variety of tumor types who have received DC-CIK therapy may experience clinical responses. This versatile therapy synergizes with other anti-cancer therapies including chemotherapy and immunotherapy.