Tim-3 mediates T cell trogocytosis to limit antitumor immunity

Pagliano, Ornella; Morrison, Randall L.; Chauvin, Joë-Marc; Banerjee, Hridesh; Davar, Diwakar; Ding, Qian; Tanegashima, Tokiyoshi; Gao, Wentao; Chakka, Saranya Rani; DeBlasio, Richelle; Lowin, Ava; Kara, Kevin; Ka, Mignane; Zidi, Bochra; Amin, Rada; Raphael, Itay; Zhang, Shuowen; Watkins, Simon C.; Sander, Cindy; Kirkwood, John M.; Bosenberg, Marcus W.; Anderson, Ana C.; Kuchroo, Vijay K.; Kane, Lawrence P.; Rajpal, Arvind; West, Sean M.; Han, Meekyung; Bee, Christine; Deng, Xiaolong; Schebye, Xiao Min; Strop, Pavel; Zarour, Hassane M.

doi:10.1172/jci152864

Cited by 32 publications

(27 citation statements)

References 52 publications

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“…T cell ability to engage trogocytosis with DCs represents a key example of how immune cells can interchange membrane molecules that may affect anti-tumor immune responses. In a recent report, expression of Tim-3 by DCs engaged its receptor phosphatidylserine on tumor-infiltrating CD8 + T cells (TILs) to promote the trogocytosis of myeloid molecules by tumor antigen-specific TILs, including pMHC-I complexes, which converted these TILs into a target for fratricide CD8 + T cell killing ( Pagliano et al., 2022 ). Moreover, trogocytic transfer of PD-L1 from human DCs to CD8 + T cells upon antigen-specific recognition endowed PD-L1 + CD8 + T cells with fratricide-killing properties ( Gary et al., 2012 ).…”

Section: Resultsmentioning

confidence: 99%

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Mattei¹,

Andreone²,

Spadaro³

et al. 2022

iScience

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Section: Resultsmentioning

confidence: 99%

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Mattei¹,

Andreone²,

Spadaro³

et al. 2022

iScience

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“…In contrast, immune suppressor cells such as Eosinophils, Fibroblasts and Macrophages M2, and HAVCR2 level were significantly higher in the CD8T‐RGPI high‐risk subgroup. Available studies indicate that Macrophages M2, tumour‐associated neutrophils and HAVCR2 are closely related to the tumour immunosuppressive microenvironment 24,43,48 . In this study, stromal as well as immune scores of HCC samples were estimated using the ESTIMATE algorithm.…”

Section: Discussionmentioning

confidence: 99%

A CD8⁺ T cell‐related genes prognostic model for hepatocellular carcinoma patients

et al. 2022

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Immune checkpoint blockade (ICB) therapy is a promising treatment for hepatocellular carcinoma (HCC). However, it is limited by low response rates. Tumour‐infiltrating immune cells (TIICs), specifically CD8+ T cells, in the tumour microenvironment (TME) are related to tumour immune responses and are potential predictors for immunotherapeutic and survival outcomes. Therefore, we established a new CD8+ T cell‐related genes prognostic index (CD8T‐RGPI) for evaluating immune responses and prognostic outcomes for HCC. Using the TCGA databases, we evaluated the RNA‐seq data of CD8+ T cell‐related genes with gene co‐expression network. Then, the CD8T‐RGPI model was built by combining univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The nomogram exhibited a good prediction ability for HCC patients' prognosis in either TCGA or ICGC databases. The CD8T‐RGPI was elevated in patients with high T, M and TNM stages. Functional enrichment analyses revealed that in CD8T‐RGPI high‐risk group, tumour‐related and immunosuppressive pathways, such as focal adhesion, aerobic glycolysis, HIF1 transcription factor pathway, IL‐4 and IL‐13 signalling were significantly enriched. Moreover, for CD8T‐RGPI high‐risk HCC patients, immune tolerance and immunosurveillance escape was associated with poor therapeutic outcomes for ICB therapy. The CD8T‐RGPI low‐risk HCC patients with elevated immune infiltration levels were associated with good immunotherapeutic responses to ICB. Our findings provide prospective prognostic biomarkers and elucidate on HCC immunotherapy.

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“…Targeting TIM-3 is another strategy based on T-cell immunotherapy. TIM-3 is an important tumor immune checkpoint expressed on a variety of immune cells including effector T cells, monocytes, NK, and DCs ( 75 , 76 ), which can inhibit innate and T-cell immune response ( 77 , 78 ), participate in immune escape ( 79 ), and promote immune tolerance ( 80 ). Blocking TIM-3 pathway can positively regulate innate and adaptive immunity, alleviate T-cell depletion, and increase the secretion of interferon-γ (IFN-γ) by NK and T cells ( 75 , 81 ).…”

Section: Tim-3mentioning

confidence: 99%

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

et al. 2022

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Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte–associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell–based therapeutic methods will be developed and applied.

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Tim-3 mediates T cell trogocytosis to limit antitumor immunity

Cited by 32 publications

References 52 publications

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

A CD8⁺ T cell‐related genes prognostic model for hepatocellular carcinoma patients

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

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Tim-3 mediates T cell trogocytosis to limit antitumor immunity

Cited by 32 publications

References 52 publications

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

A CD8+ T cell‐related genes prognostic model for hepatocellular carcinoma patients

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

Contact Info

Product

Resources

About

A CD8⁺ T cell‐related genes prognostic model for hepatocellular carcinoma patients