Tissue-Resident Memory T Cells in Cancer Immunosurveillance

Park, Simone L.; Gebhardt, Thomas; Mackay, Laura K.

doi:10.1016/j.it.2019.06.002

Cited by 142 publications

(143 citation statements)

References 145 publications

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“…Importantly, the density of T RM cells within the tumor environment has been shown to predict for improved survival in a number of cancer types, including advanced‐stage melanoma . In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models . Furthermore, we have recently demonstrated that T RM cells can promote cancer‐immune equilibrium in mouse skin by keeping dispersed melanoma cells dormant over extended periods of time .…”

Section: Introductionsupporting

confidence: 59%

“…However, T RM cells can also drive skin inflammation in the context of autoimmune diseases and tissue transplantation . Emerging clinical data further suggest that T RM cells provide immune surveillance in a variety of human cancers . Importantly, the density of T RM cells within the tumor environment has been shown to predict for improved survival in a number of cancer types, including advanced‐stage melanoma .…”

Section: Introductionmentioning

confidence: 99%

“…12 Emerging clinical data further suggest that T RM cells provide immune surveillance in a variety of human cancers. 10,13 Importantly, the density of T RM cells within the tumor environment has been shown to predict for improved survival in a number of cancer types, 7,9,10,13,14 including advanced-stage melanoma. 15 In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models.…”

Section: Introductionmentioning

confidence: 99%

“…15 In line with this, recent reports have shown that T RM cells afford potent antitumor immunity in mouse models. 10,13,[16][17][18] Furthermore, we have recently demonstrated that T RM cells can promote cancer-immune equilibrium in mouse skin by keeping dispersed melanoma cells dormant over extended periods of time. 19 Whether T RM cells have a similar function in maintaining tumor dormancy in humans, however, remains to be addressed.…”

Section: Introductionmentioning

confidence: 99%

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Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

et al. 2019

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Objective The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer‐immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. Methods Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in‐transit metastasis (ITM), the latter of which appeared as a small erythematous papule. Results Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A− melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue‐resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM‐like cells. Conclusion Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.

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Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

et al. 2019

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“…38 Indeed, despite their commonalities, tissue-resident lymphocytes may display a vast number of specific transcripts in different tissues or at different stages. 39 These findings might reflect differences in signals from the local microenvironment modulating CD103 + CD8 + formation.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis

Líu

Cao

et al. 2020

Br J Cancer

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BACKGROUND: Intratumoural CD103 + CD8 + T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103 + CD8 + T cells in gastric cancer remains unexplored. METHODS: Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103 + CD8 + T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103 + CD8 + T cells was evaluated with the use of an in vitro study based on fresh tumour tissues. RESULTS: CD103 + CD8 + T cells predicted superior overall survival and provided better prognostic power than total CD8 + T cells in gastric cancer. Patients with high CD103 + CD8 + T cell infiltration also gained more benefit from adjuvant chemotherapy. Flow cytometry analysis showed that CD103 + CD8 + T cells exerted superior anti-tumour effects with stronger retention capacity and cytotoxicity. Moreover, an in vitro study showed that CD103 + CD8 + T cells were more functionally restored after PD-1 blockade than CD103 -CD8 + T cells. CONCLUSIONS: CD103 + CD8 + T cells might be a useful marker to predict prognosis and therapeutic efficacy for gastric cancer patients. Efforts to increase intratumoural CD103 + CD8 + T cell frequency might be a novel therapeutic strategy in gastric cancer.

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Single‐cell transcriptomics reveal the intratumoral landscape of infiltrated T‐cell subpopulations in oral squamous cell carcinoma

Chen

Yang

et al. 2021

Molecular Oncology

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Systematic analysis of tumor‐infiltrating lymphocytes is essential for the development of new cancer treatments and the prediction of clinical responses to immunotherapy. Immunomodulatory drugs are used for the treatment of oral squamous cell carcinoma (OSCC), depending on immune infiltration profiles of the tumor microenvironment. In this study, we isolated 11,866 single T cells from tumors and paired adjacent normal tissues of three patients with OSCC. Using single‐cell RNA sequencing, we identified 14 distinct T‐cell subpopulations within the tumors and 5 T‐cell subpopulations in the adjacent normal tissues and delineated their developmental trajectories. Exhausted CD8+ T cells and regulatory CD4+ T cells (CD4+ Tregs) were enriched in OSCC tumors, potentially linked to tumor immunosuppression. Programmed death protein 1 (PD‐1) and cytotoxic T lymphocyte‐associated protein 4 (CTLA4) were identified as marker genes in exhausted CD8+ T cells, whereas forkhead box P3 (FOXP3) and CTLA4 were identified as markers of CD4+ Tregs. Furthermore, our data revealed that thymocyte selection‐associated high‐mobility group box (TOX) may be a key regulator of T‐cell dysfunction in the OSCC microenvironment. Overexpression of TOX upregulated expression of genes related to T‐cell dysfunction. In vitro experiments demonstrated that cytotoxic activity and proliferation efficiency of CD8+ T cells overexpressing PD‐1 or TOX were reduced. Notable, the transcription factor PRDM1 was found to transactivate TOX expression via a binding motif in the TOX promoter. Our findings provide valuable insight into the functional states and heterogeneity of T‐cell populations in OSCC that could advance the development of novel therapeutic strategies.

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Tissue-Resident Memory T Cells in Cancer Immunosurveillance

Cited by 142 publications

References 145 publications

Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis

Single‐cell transcriptomics reveal the intratumoral landscape of infiltrated T‐cell subpopulations in oral squamous cell carcinoma

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Tissue-Resident Memory T Cells in Cancer Immunosurveillance

Cited by 142 publications

References 145 publications

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis

Single‐cell transcriptomics reveal the intratumoral landscape of infiltrated T‐cell subpopulations in oral squamous cell carcinoma

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Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis

Accumulation of CD103⁺ CD8⁺ T cells in a cutaneous melanoma micrometastasis