Colorectal cancer-associated fibroblasts inhibit effector T cells via NECTIN2 signaling

Cancer Letters, Journal Year: 2024, Volume and Issue: 595, P. 216985 - 216985

Published: May 29, 2024

Cancer-associated fibroblasts play a crucial role within the tumor microenvironment. However, comprehensive characterization of CAF in colorectal cancer (CRC) is still missing. We combined scRNA-seq and spatial proteomics to decipher fibroblast heterogeneity healthy human colon CRC at high resolution. Analyzing nearly 23,000 fibroblasts, we identified 11 distinct clusters verified them by proteomics. Four clusters, consisting myofibroblastic (myCAF)-like, inflammatory (iCAF)-like proliferating as well novel cluster, which named "T cell-inhibiting CAF" (TinCAF), were primarily found CRC. This new cluster was characterized expression immune-interacting receptors ligands, including CD40 NECTIN2. Co-culture T cells resulted reduction effector cell compartment, impaired proliferation, increased exhaustion. By blocking its receptor interaction, demonstrated that NECTIN2 key driver inhibition. Analysis clinical datasets showed poor prognostic factor other tumors. In conclusion, class immuno-suppressive with features rendering potential target for future immunotherapies.

Language: Английский

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Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 614 - 614

Published: March 8, 2023

Hepatitis B virus (HBV) infection is the main risk factor for development of hepatocellular carcinoma (HCC), most common type liver cancer, with high incidence and mortality worldwide. Surgery, transplantation, ablation therapies have been used to treat early HBV-caused HCC (HBV-HCC); meanwhile, in advanced stage, chemoradiotherapy drug-targeted therapy are regularly considered, but limited efficacy. Recently, immunotherapies, such as tumor vaccine therapy, adoptive cell transfer immune checkpoint inhibitor demonstrated promising efficacy cancer treatment. In particular, inhibitors can successfully prevent tumors from achieving escape promote an anti-tumor response, thereby boosting therapeutic effect HBV-HCC. However, advantages treatment HBV-HCC remain be exploited. Here, we describe basic characteristics introduce current strategies Of note, review principles molecules, programmed death protein 1(PD-1) cytotoxic T-lymphocyte-associated 4 (CTLA-4) HBV-HCC, well related being considered clinic. We also discuss benefits those various etiologies, aiming provide insights into use

Language: Английский

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CD155 and its receptors in cancer immune escape and immunotherapy

Cancer Letters, Journal Year: 2023, Volume and Issue: 573, P. 216381 - 216381

Published: Sept. 3, 2023

Language: Английский

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CD8+ CD226high T cells in liver metastases dictate the prognosis of colorectal cancer patients treated with chemotherapy and radical surgery

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(4), P. 365 - 378

Published: Jan. 30, 2023

CD226 has been reported to participate in the rescue of CD8+ T cell dysfunction. In this study, we aimed assess prognostic value tumor-infiltrating lymphocytes (TILs) derived from colorectal cancer (CRC) liver metastases treated with chemotherapy and radical surgery. TILs 43 were isolated analyzed ex vivo using flow cytometry. CD155 CD3 levels tumor microenvironment assessed by immunohistochemistry. Exploration validation biological processes highlighted study performed bioinformatics analysis bulk RNA-seq results for 28 CRC pretreated as well public gene expression datasets. contributes definition immune context primary tumors. on cells was not specifically coexpressed other checkpoints, such PD1, TIGIT, TIM3, metastases. Multivariate Cox regression revealed be an independent factor (p = 0.003), along density at invasion margins 0.003) TIGIT CD4+ 0.019). associated CD226. Gene a dataset confirmed but Downregulation restored IL15 treatment. Overall, metastasis-infiltrating selectively surveillance patients undergoing

Language: Английский

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TIGIT: An emerging immune checkpoint target for immunotherapy in autoimmune disease and cancer

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 120, P. 110358 - 110358

Published: May 31, 2023

Language: Английский

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