Tumor-Infiltrating T Cells — A Portrait

Braun, David A.; Wu, Catherine J.

doi:10.1056/nejmcibr2119477

Cited by 12 publications

(10 citation statements)

References 6 publications

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“…T cells are an important component of the human immune system. T cell receptors are responsible for initiating signaling pathways that activate, inactivate or eliminate T cells and alterations in T cell-positive/negative regulatory factors can inhibit T cell function and mediate immune escape [ 127 , 128 ]. Methylation of m 6 A affects T cells in multiple ways (including signaling pathways and glycolytic metabolism), leading to profound effects on T cell differentiation and function and generation of an immunosuppressive environment to facilitate tumor evasion of immune surveillance [ 70 , 129 ].…”

Section: A Methylation Remodels Immunosuppressive Tme By Directly Aff...mentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

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The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.

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Section: A Methylation Remodels Immunosuppressive Tme By Directly Aff...mentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

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“…Infiltrating immune cells in tumor tissues have also been a hot topic [ 58 , 59 ]. By performing a retrospective analysis of the status of TILs in patients with different therapeutic responses, we found that after treatment, the densities of cytotoxic T cells, Tregs and PD-1 + Tregs were all significantly different in the resection tissues of patients in the pCR group and non-pCR group.…”

Section: Discussionmentioning

confidence: 99%

T-cell subsets and cytokines are indicative of neoadjuvant chemoimmunotherapy responses in NSCLC

Yi,

Xu,

et al. 2024

Cancer Immunol Immunother

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Purpose Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. Methods Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry. Cytokine profiles and function-related gene expression of CD8 + T cells and Tregs were analyzed through flow cytometry and mRNA-seq. Infiltrating T-cell subsets in resected tissues from patients with different pathological responses were analyzed through multiplex immunofluorescence. Results Forty-two NSCLC patients receiving neoadjuvant chemoimmunotherapy were enrolled and then underwent surgical resection and pathological evaluation. Nineteen patients had pCR (45%), 7 patients had MPR (17%), and 16 patients had non-MPR (38%). In patients with pCR, the frequencies of CD137 + CD8 + T cells (P = 0.0475), PD-1 + Ki-67 + CD8 + T cells (P = 0.0261) and Tregs (P = 0.0317) were significantly different from those of non-pCR patients before treatment. pCR patients usually had low frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs, and their AUCs were higher than that of tissue PD-L1 expression. Neoadjuvant chemoimmunotherapy markedly improved CD8 + T-cell proliferation and activation, especially in pCR patients, as the frequencies of CD137 + CD8 + (P = 0.0136) and Ki-67 + CD8 + (P = 0.0391) T cells were significantly increased. The blood levels of cytokines such as IL-2 (P = 0.0391) and CXCL10 (P = 0.0195) were also significantly increased in the pCR group, which is consistent with the high density of activated cytotoxic T cells at the tumor site (P < 0.0001). Conclusion Neoadjuvant chemoimmunotherapy drives CD8 + T cells toward a proliferative and active profile. The frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs at baseline might predict the response to neoadjuvant chemoimmunotherapy in NSCLC patients. The increase in IL-2 and CXCL10 might reflect the chemotaxis and enrichment of cytotoxic T cells at the tumor site and a better response to neoadjuvant chemoimmunotherapy.

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“…However, radiation treatment modality, detection methods, and tumor models may contribute to the discrepancy in immune cell infiltration. Moreover, immune cell subsets should be clarified and compared because they function differently [32] .…”

Section: Discussionmentioning

confidence: 99%

Comparison of intratumor and local immune response between MV X-ray FLASH and conventional radiotherapies

Zhu

Xie

Wang

et al. 2023

Clinical and Translational Radiation Oncology

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Tumor-Infiltrating T Cells — A Portrait

Cited by 12 publications

References 6 publications

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

T-cell subsets and cytokines are indicative of neoadjuvant chemoimmunotherapy responses in NSCLC

Comparison of intratumor and local immune response between MV X-ray FLASH and conventional radiotherapies

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