Tumor infiltrating and peripheral CD4+ILT2+ T cells are a cytotoxic subset selectively inhibited by HLA-G in clear cell renal cell carcinoma patients

Jacquier, Alix; Lambert, Tiphaine; Delattre, Jean-François; Djouadou, Malika; Verine, Jérôme; Dumont, Clément; Desgrandchamps, François; Carosella, Edgardo D.; LeMaoult, Joël; Rouas‐Freiss, Nathalie

doi:10.1016/j.canlet.2021.06.018

Cited by 13 publications

(5 citation statements)

References 47 publications

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“…If the ratio decreases, the patient's immune function is in a low state, and the proliferation and spread of the tumor will be enhanced. Therefore, the infiltration of CD4+ T lymphocytes in adjacent tissues and the changes in peripheral blood can reflect the development trend of tumors to a certain extent [ 12 – 15 ]. In this study, we found that in COAD patients with high INSC expression, the levels of various immune lymphocytes increased, which may be an explanation for the better prognosis of these patients.…”

Section: Discussionmentioning

confidence: 99%

INSC Is a Prognosis-Associated Biomarker Involved in Tumor Immune Infiltration in Colon Adenocarcinoma

Weidong

2022

BioMed Research International

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Aims. The purpose of this study was to investigate the correlation of INSC gene with the level of immune infiltration and clinical prognosis in colon adenocarcinoma (COAD) patients. Materials and Methods. INSC expression profile data and clinicopathological information of COAD patients were downloaded from TCGA. Xiantao bioinformatics tool was used to analyze the expression of INSC between the COAD group and the normal control group, and GEPIA2 was used to analyze the top 100 coexpressed genes. Logistic regression analysis was performed to assess the relationship between clinicopathological features and INSC. The Kaplan-Meier method and Cox regression model were used to perform the survival analysis. CIBERSORT algorithm was used to analyze the relationship between INSC expression and immune infiltration cells. Results. The expression level of INSC in COAD was significantly downregulated. The result of logistic regression analysis confirmed that tumor stage was the final influencing factor of INSC expression. The overall survival rate of INSC in the high expression group was higher than that of the low expression group, and it was an independent risk factor of prognosis. Enrichment results indicated that INSC was enriched in the regulation of T-helper 2 cell differentiation pathway. Immune infiltration analysis showed that INSC expression was positively correlated with the B cell plasma, T cell CD4+ memory resting, activated myeloid dendritic cells, and eosinophils. Conclusions. Our study found that the expression of INSC was significantly downregulated in COAD, which regulated immune-infiltrating cells during cancer development and was associated with malignant progression in COAD patients.

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Section: Discussionmentioning

confidence: 99%

INSC Is a Prognosis-Associated Biomarker Involved in Tumor Immune Infiltration in Colon Adenocarcinoma

Weidong

2022

BioMed Research International

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“…IFN-γ upregulates the expression of MHC II and increases the cytotoxic effect of CD4+ CTLs on tumor cells [ 134 ]. The blockade of HLA-G/CD85j increases the cytolytic activity of CD4+ CTLs to improve the antitumor immune responses [ 135 , 136 ]. Tregs utilize IL-2 deprivation to inhibit T-cell-mediated cellular immunity, whereas endogenous IL-2 drives the upregulation of the transcription factor Blimp-1 within CD4+ Th cells to further promote granzyme B expression, and Tregs may compete with IL-2 to negatively control this process [ 73 ].…”

Section: Improving the Cytotoxic Function Of Ctlsmentioning

confidence: 99%

CTLs heterogeneity and plasticity: implications for cancer immunotherapy

Peng,

Lin,

Jiang

et al. 2024

Mol Cancer

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Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ T cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. CTLs differentiation involves transcriptional regulation by factors such as T-bet and Blimp-1, although epigenetic regulation of CTLs is less clear. CTLs promote tumor killing through cytotoxic granules and death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that CTLs cytotoxicity varies across tumors, enhancing this function is critical. This review summarizes current knowledge on CTLs subsets, biomarkers, differentiation mechanisms, cancer-related functions, and strategies for improving cytotoxicity. Key outstanding questions include refining the CTLs definition, characterizing subtype diversity, elucidating differentiation and senescence pathways, delineating CTL-microbe relationships, and enabling multi-omics profiling. A more comprehensive understanding of CTLs biology will facilitate optimization of their immunotherapy applications. Overall, this review synthesizes the heterogeneity, regulation, functional roles, and enhancement strategies of CTLs in antitumor immunity, highlighting gaps in our knowledge of subtype diversity, definitive biomarkers, epigenetic control, microbial interactions, and multi-omics characterization. Addressing these questions will refine our understanding of CTLs immunology to better leverage cytotoxic functions against cancer.

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“…HLA-G has the ability to inhibit T lymphocyte cytotoxicity and the proliferation of allogeneic CD4 + T cells [ 130 , 131 ]. Significantly, the receptor ILT2, which exhibits a high affinity for HLA-G, is expressed on the surface of certain CD4 + and CD8 + T cells [ 132 , 133 ].…”

Section: Hla-g and Immune Cells At The Maternal–fetal Interfacementioning

confidence: 99%

The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

Mao,

Feng,

Zhu

et al. 2023

Biomolecules

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Human leukocyte antigen-G (HLA-G) is a non-classical human major histocompatibility complex (MHC-I) molecule with the membrane-bound and soluble types. HLA-G is primarily expressed by extravillous cytotrophoblast cells located at the maternal–fetal interface during pregnancy and is essential in establishing immune tolerance. This review provides a comprehensive understanding of the multiple molecular mechanisms by which HLA-G regulates the immune function of NK cells. It highlights that HLA-G binds to microRNA to suppress NK cell cytotoxicity and stimulate the secretion of growth factors to support fetal growth. The interactions between HLA-G and NK cells also activate senescence signaling, promoting spiral artery remodeling and maintaining the balance of maternal–fetal immune responses. In addition, HLA-G can inhibit the function of decidual T cells, dendritic cells, and macrophages. Overall, the interaction between trophoblast cells and immune cells mediated by HLA-G plays a crucial role in understanding immune regulation at the maternal–fetal interface and offers insights into potential treatments for pregnancy-related diseases.

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Tumor infiltrating and peripheral CD4+ILT2+ T cells are a cytotoxic subset selectively inhibited by HLA-G in clear cell renal cell carcinoma patients

Cited by 13 publications

References 47 publications

INSC Is a Prognosis-Associated Biomarker Involved in Tumor Immune Infiltration in Colon Adenocarcinoma

INSC Is a Prognosis-Associated Biomarker Involved in Tumor Immune Infiltration in Colon Adenocarcinoma

CTLs heterogeneity and plasticity: implications for cancer immunotherapy

The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

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