2017
DOI: 10.1038/ni.3775
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Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer

Abstract: Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of mole… Show more

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Cited by 403 publications
(466 citation statements)
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“…Additionally, T RM cells are necessary for the efficacy of cancer vaccine [11, 33]. The protective effect of T RM cells in cancer is linked to their high degree of cytotoxicity, which is correlated with the magnitude of their perforin and granzyme expression [14]. In spite of expressing cytotoxic mediators, T RM cells in the tumour express the exhaustion markers PD‐1, T cell immunoglobulin and mucin domain 3 (TIM‐3) and lymphocyte‐activation gene 3 (LAG‐3) [34].…”
Section: Discussionmentioning
confidence: 99%
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“…Additionally, T RM cells are necessary for the efficacy of cancer vaccine [11, 33]. The protective effect of T RM cells in cancer is linked to their high degree of cytotoxicity, which is correlated with the magnitude of their perforin and granzyme expression [14]. In spite of expressing cytotoxic mediators, T RM cells in the tumour express the exhaustion markers PD‐1, T cell immunoglobulin and mucin domain 3 (TIM‐3) and lymphocyte‐activation gene 3 (LAG‐3) [34].…”
Section: Discussionmentioning
confidence: 99%
“…Notably, the cytotoxic activity of CD8 + T cells is initiated by perforin forming the pore that allows granzymes to enter and induce apoptosis of the tumour cells [13]. In contrast, T RM cells residing in the tumour tissue have been demonstrated to express programmed cell death 1 (PD‐1), suggesting exhaustion [14]. In this context, the phenotype of T RM cells displaying simultaneous cytotoxicity and exhaustion markers needs further study.…”
Section: Introductionmentioning
confidence: 99%
“…Expression by CD8 + CD103 + TIL of granzyme B, perforin and the degranulation marker LAMP-1 (CD107a) was confirmed at the protein level, further supporting their cytotoxic potential [27, 38, 64]. Moreover, in ovarian and lung cancer, T RM cells express the activation marker HLA-DR and the proliferation marker Ki67 [38, 64]. These cells may be functionally exhausted within the tumor microenvironment by the induction of T-cell inhibitory receptors including PD-1 and Tim-3 [27].…”
Section: Mechanisms Of Action Of Trm Cellsmentioning
confidence: 96%
“…T RM cells do not express CCR7, CD62L or S1PR1 [14, 27, 38], which are required for tissue exit (Fig. 1).…”
Section: Phenotypic Features Of Trm Cells In Cancermentioning
confidence: 99%
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