CD8 (cluster of differentiation 8)

Tumor microenvironment changes of consistently low T cells, low CD4+ T cells, and high PD-L1 were independent predictors of poor OS in multivariate Cox hazards analyses, while factors indicating post-NAC status (T cells, CD4+, and PD-L1 [CPS]) alone were not. Therefore, we suggest that the consistently low T/high PD-L1 group could benefit from additional therapies, such as ICIs, and the importance of stratification by the TME, which has recently been recognized.

Cytokine secretion patterns, antigen uptake, antigen proteolysis and antigen presenting function differed between WT and Flt3ITD/ITD subsets, particularly cDC2. In summary, Flt3 signaling impacts the function of terminally differentiated cDCs with important consequences for antigen presentation.

P=N/A, N=400, Recruiting, Columbia University | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=10, Recruiting, City of Hope Medical Center | Trial completion date: Apr 2024 --> Oct 2025 | Trial primary completion date: Apr 2024 --> Oct 2025

We also discuss the mechanisms underlying how specific nutrient sources and metabolite-mediated signaling events orchestrate CTL biology. Understanding how metabolic programs and their interplay with immune signals instruct CTL differentiation and exhaustion is crucial to uncover tumor-immune interactions and design novel immunotherapies.

This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H.

In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69). Notably, no histologic signs of allograft rejection are observed in consecutive end-myocardial biopsies. These findings provide valuable insights into the dynamics of T cell activation and differentiation and suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T cell function while maintaining allograft tolerance.

The groups that received pDNA/tachyplesin exhibited a substantial upregulation in the expression levels of caspase-3, caspase-8, BAX, PI3K, STAT3, and JAK genes. The results offer new possibilities for treating cancer by targeting malignancies using pDNA/tachyplesin and activating the mTOR and NFκB signaling pathways.

We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.

TKI-induced SM+ cells could stimulate or suppress CD8 T-cell activation depending on host:tumor cell contact while tumors grown from SM+ cells were more sensitive to PD-L1 inhibition in vivo, suggesting that offsetting immune-suppressive functions of SM+ cells can improve TKI efficacy overall. Our findings may explain why some (but not all) VEGFR TKIs improve outcomes when combined with immunotherapy and suggest that exploiting senomimetic drug side-effects may help identify TKIs that uniquely 'prime' tumors for enhanced sensitivity to PD-L1 targeted agents.

P=N/A, N=800, Not yet recruiting, Midway Specialty Care Center

MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Further characterization of the CD3+, CD8+, and other cells is also warranted. In the future, this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.

To our knowledge, < 20 patients of primary cutaneous acral CD8-positive lymphoproliferative disorder with a nonacral presentation have been described in English literature. Although rare, its identification is essential to differentiate it from other T-cell lymphoma that express CD8 and cytotoxic markers, and whose clinical courses are very aggressive.

QuPath showed a strong correlation with manual counting, confirming its utility and accuracy and potential applicability in clinical practice.

Compared with traditional strategies, for the first time, we demonstrated that a triple treatment strategy remarkably increased the number of radiation-induced tumor-infiltrating CD8 + T-cells, effectively decreasing infiltrating Tregs, and promoting an abscopal effect. Thus, we describe a novel and effective therapeutic approach by combining multiple strategies to target several tumor-mediated immune inhibitory mechanisms.

CD8 TSL cells were observed in patients with stages I-III LUAD and might serve as prognostic biomarkers for stage I LUAD.

Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8+ T cells. FOXP4-AS1 suppressed the viability and abundance of CD8+ T cells through USP10-mediated deubiquitination of PD-L1.

The immune cell signature, comprising SDC-1, PLAUR, FN1, and CXCL13, holds promise as a predictive tool for assessing glioblastoma prognosis following radiotherapy. This signature also offers valuable guidance for tailoring treatment strategies, emphasizing its potential clinical relevance in improving patient outcomes.

The results indicate that APG-157 and immune checkpoint inhibitor combination treatment could potentially lead to improved tumor control.

• Applicable to TCRs from CD8+ and CD4+ tumor-infiltrating T-cells originating from patient-derived tumor samples and syngeneic mouse tumor models. • Rapid flow cytometric detection of T-cell activation by means of TNFα and CD107a expression after a 5 h T-cell/tumor cell co-cultivation.

Clonally expanded CD8+ T cells in responding tumours post ICT displayed effector T cell gene signatures and phenotype. An early burst of clonal expansion during ICT is associated with response, and we report unique dynamics in TCRβ signatures associated with ICT response.

In vitro, PD-L1 is inhibited by the overexpression of menin. Mechanistically, we found that MEN1 inactivation promotes the deubiquitinating activity of COP9 signalosome subunit 5 (CSN5) and subsequently increases the level of PD-L1.

The structuring of gut flora plays a pivotal role in augmenting the efficacy of anti-tumor immunotherapy, underscoring the interplay between intestinal microecology and immune response in cancer treatment outcomes.

The findings suggest the combination of PD-1-inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow-up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.

Co-delivery of Xkr8 small interference RNA (siRNA) and a prodrug conjugate of 5-fluorouracil (5-Fu) and oxoplatin (FuOXP) showed remarkable therapeutic efficacy in an orthotopic pancreatic tumor model with increased infiltration of proliferative NK cells and activated macrophages in the tumor microenvironment (TME). Single-cell trajectory analysis further unveiled that tumor infiltrating CD8+ T cells are differentiated favorably to cytotoxic over exhausted phenotype after combination treatment. Our study sheds new light on the impact of Xkr8 knockdown on TME and solidifies the rationale of combining Xkr8 knockdown with chemotherapy to treat various types of cancers.

WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM+DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

Moreover, FABP5 inhibition induces a pro-inflammatory tumour microenvironment characterized by tumour-associated macrophages with increased expression of the co-stimulatory molecules CD80 and CD86 and increased CD8+ T cell activation. Our work unravels the dual functional role of FABP5 in diet-induced HCC, inducing the transformation of hepatocytes and an immunosuppressive phenotype of tumour-associated macrophages and illustrates FABP5 inhibition as a potential therapeutic approach.

P1, N=20, Recruiting, Medical University of South Carolina | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Jun 2024

We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell-cell communication in the tumor microenvironment.

Predictive plots were constructed to demonstrate survival estimates, combining CD8 Tex cell gene markers and clinical factors. This study provides valuable insights into the molecular and immune characteristics of osteosarcoma and offers potential avenues for advances in therapeutic approaches.

Results from an enrichment analysis indicated that SPTBN2 may regulate the development of PAAD via immune pathways. Thus, SPTBN2 is a potential prognostic biomarker and immunotherapy target based on its crucial role in the development of PAAD.

In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

HA-1 TCR-T therapy appears feasible and safe and shows preliminary signals of efficacy. This clinical trial is registered at clinicaltrials.gov as NCT03326921.

This study highlights the superior efficacy of anti-BCMA-CAR3 T cells against both low and high BCMA-expressing MM cells, surpassing anti-BCMA-CAR2 T cells. These findings suggest potential for advancing anti-BCMA-CAR3 T cells in chimeric antigen receptor T (CAR-T) therapy for relapsed/refractory MM.

Furthermore, we briefly discuss the main inborn errors of immunity that compromise cytotoxic responses by NK and CD8+ T cells, and how this scenario affects the antiviral response during EBV infection. Finally, we conclude the review by underlying the need for an effective EBV vaccine capable of preventing infection and the consequent development of malignancies and autoimmune diseases.

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months)...Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.

FOXA1 up-regulated the expression of UBE2T, which activated glycolysis, and thus inhibited activity of CD8+T cells, causing immune escape of LUAD.

In conclusion, the findings of the present study indicate that YTHDF1 is associated with a poor prognosis and serves an important role in the TME of GC. We hypothesize, for the first time to the best of our knowledge, that YTHDF1 regulates immune cell infiltration by interacting with p53 in GC, which provides a promising direction for future research.

In summary, our pioneering approach involving the silicasome carrier not only improved antitumor angiogenesis but also profoundly reshaped the desmoplastic stromal and immune landscape within PDAC. These insights hold excellent promise for the development of innovative combinatorial strategies in PDAC therapy.

Finally, the HuR inhibitor pyrvinium pamoate lowers tumor burden by enhancing CD8+ infiltration at the expense of CD4+, suggesting anticancer benefits. Thus, HuR-dependent oral neoplasia relies on immunological dysfunction, suggesting that decreasing HuR may boost antitumor potential and offer a novel HNSCC therapy.

Additionally, Patients in the low-risk group might have superior responses to chemotherapy and immunotherapy. Conclusively, this study created a new risk model based on genes associated with NAS pathways which could predict the prognosis and response of treatment in patients with SCLC.