Role of CD8+ T lymphocyte cells: Interplay with stromal cells in tumor microenvironment

Xie, Qin; Ding, Jian; Chen, Yi

doi:10.1016/j.apsb.2021.03.027

Cited by 59 publications

(46 citation statements)

References 162 publications

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“…A previous article reported that fibroblasts with somatic copy number alterations in the TME play synergetic roles in tumor development through complex interactions with cancer cells, and RCN3 is identified as a fibroblast-specific biomarker of poorer prognosis of colorectal cancer (CRC) ( 21 ). In contrast, the tumor-infiltrating lymphocytes (TLSs), CD8 + T lymphocytes, play a pivotal role in survival prognosis, tumor regression, and antitumor immunity, through weakening CD8 + T cell activation, immunosuppressive factors in TME maintain tumor immune inhibition status ( 37 – 39 ). Thus, TAMs and CAFs are potential target cells for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy

et al. 2022

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Despite emerging publications have elucidated a functional association between RCN3 and tumors, no evidence about a pan-cancer analysis of RCN3 is available. Our study first conducted a comprehensive assessment of its expression profiles, prognosis value, immune infiltration, and relevant cellular pathways via bioinformatics techniques based on the public database of TCGA (The Cancer Genome Atlas). RCN3 is highly expressed in most tumors, and it is associated with poor prognosis. Kaplan-Meier analysis and Cox regression analysis suggested that the high expression of RCN3 was associated with poor overall survival (OS) in pan-cancer, Cox regression analysis also indicated high RCN3 expression was correlated with disease-specific survival (DSS) and progression-free interval (PFI) in most tumors. We observed a regulation function of RCN3 at genetic and epigenetic levels through CNA and DNA methylation using cBioPortal database. Based on Gene Set Enrichment Analysis, we first identified related pathways of RCN3 and its potential biological functions in pan-cancer, RCN3 was implicated in oncogenic pathways, and was related to extracellular matrix and immune regulation. We found that RCN3 positively correlated with the levels of infiltrating cells such as TAMs and CAFs, but negatively correlated with CD8+ T-cells by analyzing immune cell infiltration data we downloaded from published work and online databases, further investigation of the correlation between immunosuppressive genes, chemokines, chemokines receptors, and high RCN3 expression showed a significant positive association in the vast majority of TCGA cancer types. These results indicated its role as an immune regulatory in cancers and suggested that RCN3 is a potential biomarker for immunotherapy. Also, we found that expression of RCN3 was much higher in CRC tissues than in normal tissues with a higher expression level of RCN3 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size, and poor prognosis of CRC. Biological function experiments showed that RCN3 regulated CRC cells’ proliferation and metastasis ability. Upregulation of RCN3 in CRC cells increased the expression of immune related factor, including TGFβ1, IL-10, and IL-6. Thus, our pan-cancer analysis offers a deep understanding of potential oncogenic roles of RCN3 in different cancers.

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Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy

et al. 2022

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“…As a highly mutated cancer, CRC progressively loses its tumor antigen and MHC‐1 contents until immune escape prevails 6 . Obesity tends to aid immune escape by conferring T cell populations with exhausted phenotypes 7 . Exhausted T cells are a discrete T cell subset characterized by progressive loss of effector cytokines and impaired cytotoxicity 8 .…”

Section: Introductionmentioning

confidence: 99%

“… 6 Obesity tends to aid immune escape by conferring T cell populations with exhausted phenotypes. 7 Exhausted T cells are a discrete T cell subset characterized by progressive loss of effector cytokines and impaired cytotoxicity. 8 Actually, Tex represent a hyporesponsive state that stems from adaptation to persistent antigen and chronic T cell receptor stimulation.…”

Section: Introductionmentioning

confidence: 99%

Dahuang Fuzi Baijiang decoction restricts progenitor to terminally exhausted T cell differentiation in colorectal cancer

Wang

et al. 2022

Cancer Science

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Obesity increases the risk of colorectal cancer (CRC) by 30%. The obese tumor microenvironment compromises antitumor immunity by eliciting exhausted T cells (Tex). Hypothesizing that Dahuang Fuzi Baijiang decoction (DFB) is a combined classical prescription from the “Synopsis of Prescriptions of the Golden Chamber”. We first determined that DFB regresses tumor growth in high‐fat diet–induced obese mice by expanding the TIM3− subset with intermediate expression of programmed cell death‐1 (PD‐1intTIM3−) and restricting the PD‐1hiTIM3+ subset. Transcription factor 1 (TCF1) is highly expressed in the PD‐1intTIM3− subset but is absent in PD‐1hiTIM3+ cells. We next confirmed that progenitor PD‐1intTCF+ cells robustly produce tumor necrosis factor‐α (TNFα) and interferon‐γ, whereas terminally differentiated PD‐1intTCF+ cells have defects in generating TNFα. With transgenic ob/ob mice, we found that DFB produces cooperative efficacy with anti‐PD‐1 (αPD‐1) by limiting the PD‐1hiTim3+ subset and amplifying the PD‐1intTCF+ population. Finally, we defined the recombinant chemokine C‐C‐motif receptor 2 (CCR2)+CD8+ subset as terminal Tex and identified that the differentiation from progenitor to terminal Tex is driven, at least in part, by the chemokine (C‐C motif) ligand 2 (CCL2)/CCR2 axis. The CCR2 inhibitor enhances the response to αPD‐1 by promoting the counts of progenitor Tex. Altogether, DFB dampens CCL2 and preserves progenitor Tex in the obese microenvironment to restrain CRC progression. These findings provide unambiguous evidence that the traditional Chinese formula DFB can prevent tumor progression by modulating adaptive immunity and establish a strong rationale for further clinical verification.

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“…Since stromal cells in the TME express cytokines and immunological factors, it is critical to consider stromal cells to rescue tumor-reactive CD8 + T cells from immune evasion mechanisms ( 80 ). According to a study by Lakins et al., CAF-educated T cells can induce death of T cells by PD-L2 and Fas ligand (FasL) engagement in the lung tumor stroma ( 81 ).…”

Section: The Pro-tumorigenic Effect Of the Relationship Between Strom...mentioning

confidence: 99%

Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

et al. 2022

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The tumor microenvironment (TME) plays a critical role in tumorigenesis and is comprised of different components, including tumor cells, stromal cells, and immune cells. Among them, the relationship between each mediator involved in the construction of the TME can be understood by focusing on the secreting or expressing factors from each cells. Therefore, understanding the various interactions between each cellular component of the TME is necessary for precise therapeutic approaches. In carcinoma, stromal cells are well known to influence extracellular matrix (ECM) formation and tumor progression through multiple mediators. Immune cells respond to tumor cells by causing cytotoxicity or inflammatory responses. However, they are involved in tumor escape through immunoregulatory mechanisms. In general, anti-cancer therapy has mainly been focused on cancer cells themselves or the interactions between cancer cells and specific cell components. However, cancer cells directly or indirectly influence other TME partners, and members such as stromal cells and immune cells also participate in TME organization through their mutual communication. In this review, we summarized the relationship between stromal cells and immune cells in the TME and discussed the positive and negative relationships from the point of view of tumor development for use in research applications and therapeutic strategies.

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Role of CD8+ T lymphocyte cells: Interplay with stromal cells in tumor microenvironment

Cited by 59 publications

References 162 publications

Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy

Pan-Cancer Analysis of the Oncogenic and Immunological Role of RCN3: A Potential Biomarker for Prognosis and Immunotherapy

Dahuang Fuzi Baijiang decoction restricts progenitor to terminally exhausted T cell differentiation in colorectal cancer

Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

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