Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells

Enamorado, Michel; Iborra, Salvador; Priego, Elena; Cueto, Francisco J.; Quintana, Juan A.; Martínez-Cano, Sarai; Mejías-Pérez, Ernesto; Esteban, Mariano; Melero, Ignacio; Hidalgo, Andrés; Sancho, David

doi:10.1038/ncomms16073

Cited by 230 publications

(248 citation statements)

References 40 publications

(86 reference statements)

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“…Tumor cells were dynamically surveyed by CD69 + CD103 + CD8 + T RM cells, and T RM cell responses were observed more often and at higher densities in peritumoral skin than in the skin of tumor‐bearing mice. In line with the findings of Enamorado et al (), melanoma development was also suppressed in the majority of mice, irrespective of depletion of T CIRC cells, but protection was most pronounced in mice harboring both T CIRC and T RM cells. These studies clearly affirm the potential of intradermal vaccine‐induced T RM cells to achieve potent protection against skin cancer.…”

Section: Skin‐resident T‐cell Responses In Melanomasupporting

confidence: 90%

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Willemsen

Linkutė

Luiten

et al. 2019

Pigment Cell Melanoma Res

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Tissue‐resident memory T (TRM) cells are abundant in the memory T cell pool and remain resident in peripheral tissues, such as the skin, where they act as alarm sensors or cytotoxic killers. TRM cells persist long after the pathogen is eliminated and can respond rapidly upon reinfection with the same antigen. When aberrantly activated, skin‐located TRM cells have a profound role in various skin disorders, including vitiligo and melanoma. Autoreactive TRM cells are present in human lesional vitiligo skin and mouse models of vitiligo, which suggests that targeting these cells could be effective as a durable treatment strategy for vitiligo. Furthermore, emerging evidence indicates that induction of melanoma‐reactive TRM cells is needed to achieve effective protection against tumor growth. This review highlights seminal reports about skin‐resident T cells, focusing mainly on their role in the context of vitiligo and melanoma, as well as their potential as therapeutic targets in both diseases.

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Section: Skin‐resident T‐cell Responses In Melanomasupporting

confidence: 90%

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Willemsen

Linkutė

Luiten

et al. 2019

Pigment Cell Melanoma Res

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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%

“…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%

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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“…Lastly, in a parabiosis mouse model, one of our groups showed that T RM cells induced by intranasal vaccination are required to control orthotopic head and neck tumor growth [39]. These results obtained with parabiosis experiments have been reproduced by the group of Sancho [10]. Together, these observations suggest that the absence of local T RM induction correlates with lower vaccine efficiency; they highlight the crucial role of these cells in tumor control.…”

Section: Role Of Trm In Immune Surveillance and Immunotherapymentioning

confidence: 81%

Resident memory T cells, critical components in tumor immunology

Mami‐Chouaib¹,

Blanc²,

Corgnac³

et al. 2018

j. immunotherapy cancer

227

186

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CD8+ T lymphocytes are the major anti-tumor effector cells. Most cancer immunotherapeutic approaches seek to amplify cytotoxic T lymphocytes (CTL) specific to malignant cells. A recently identified subpopulation of memory CD8+ T cells, named tissue-resident memory T (TRM) cells, persists in peripheral tissues and does not recirculate. This T-cell subset is considered an independent memory T-cell lineage with a specific profile of transcription factors, including Runx3+, Notch+, Hobit+, Blimp1+, BATF+, AHR+, EOMESneg and Tbetlow. It is defined by expression of CD103 (αE(CD103)β7) and CD49a (VLA-1 or α1β1) integrins and C-type lectin CD69, which are most likely involved in retention of TRM cells in non-lymphoid tissues, including solid tumors. CD103 binds to the epithelial cell marker E-cadherin, thereby favoring the location and retention of TRM in epithelial tumor regions in close contact with malignant cells. The CD103-E-cadherin interaction is required for polarized exocytosis of lytic granules, in particular, when ICAM-1 expression on cancer cells is missing, leading to target cell death. TRM cells also express high levels of granzyme B, IFNγ and TNFα, supporting their cytotoxic features. Moreover, the local route of immunization targeting tissue dendritic cells (DC), and the presence of environmental factors (i.e. TGF-β, IL-33 and IL-15), promote differentiation of this T-cell subtype. In both spontaneous tumor models and engrafted tumors, natural TRM cells or cancer-vaccine-induced TRM directly control tumor growth. In line with these results, TRM infiltration into various human cancers, including lung cancer, are correlated with better clinical outcome in both univariate and multivariate analyses independently of CD8+ T cells. TRM cells also predominantly express checkpoint receptors such as PD-1, CTLA-4 and Tim-3. Blockade of PD-1 with neutralizing antibodies on TRM cells isolated from human lung cancer promotes cytolytic activity toward autologous tumor cells. Thus, TRM cells appear to represent important components in tumor immune surveillance. Their induction by cancer vaccines or other immunotherapeutic approaches may be critical for the success of these treatments. Several arguments, such as their close contact with tumor cells, dominant expression of checkpoint receptors and their recognition of cancer cells, strongly suggest that they may be involved in the success of immune checkpoint inhibitors in various cancers.

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Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells

Cited by 230 publications

References 40 publications

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

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

Resident memory T cells, critical components in tumor immunology

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Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells

Cited by 230 publications

References 40 publications

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

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

Resident memory T cells, critical components in tumor immunology

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