Resident Memory T Cells as Surrogate Markers of the Efficacy of Cancer Vaccines

Nizard, Mevyn; Roussel, H.; Tartour, Éric

doi:10.1158/1078-0432.ccr-15-2364

Cited by 26 publications

(19 citation statements)

References 15 publications

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“…Moreover, other immunostimulatory antibodies, such as anti-CD137, could also enhance the resident memory response38. In conclusion, our results support the notion that anti-tumour vaccination strategies should aim at the generation of both circulating and resident memory CD8 + T-cell subsets222339, which could synergize with checkpoint antibody therapy for improved cancer immunotherapy.…”

Section: Discussionsupporting

confidence: 79%

“…Previous studies in human cancer show that the infiltration of tumours by T cells with a Trm cell-like phenotype correlates with improved overall survival in early stage non-small-cell lung carcinoma, pulmonary squamous cell carcinoma and high-grade serous epithelial ovarian cancer192021. In addition, recent results suggest that vaccination routes that promote generation of Trm cells could be more effective for anti-tumour response2223. These findings prompted us to analyse the relative contribution and plasticity of circulating memory CD8 + T cells and Trm cells in a model of anti-tumour vaccination.…”

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confidence: 99%

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

et al. 2017

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The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8+ T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8+ T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy. Transferred central memory T cells (Tcm) generate Trm cells following viral infection or tumour challenge. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Moreover, Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Our findings show the plasticity, collaboration and requirements for reactivation of memory CD8+ T cells subsets needed for optimal tumour vaccination and immunotherapy.

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

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

et al. 2017

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“…Indeed, mucosal, but not systemic, routes (intramuscular), generate a potent local T-cell response with a T RM phenotype, in parallel with a systemic response. For example, multiple studies, especially in an infectious context, have shown that tissue-specific vaccination is more effective at generating local immunity and T RM cells at barrier sites because it favors homing of immune cells to local sites [74]. In the same manner, heterologous prime-boost strategy with a cervico-vaginal boost enhances the establishment of specific CD8 + T cells expressing α 4 β 7 integrin in the genital tract compared to an intramuscular boost [67].…”

Section: Priming Of Trm Cells In Normal and Tumoral Tissuesmentioning

confidence: 99%

Resident memory T cells, critical components in tumor immunology

Mami‐Chouaib¹,

Blanc²,

Corgnac³

et al. 2018

j. immunotherapy cancer

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214

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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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“…Dans des modèles précliniques, notre groupe a montré que, pour les tumeurs de localisation muqueuse, ces vaccins pourraient être amélio-rés en induisant une immunité pas seulement dans le sang des patients mais aussi au niveau du site tumoral muqueux [29]. Les voies muqueuses d'immunisation (intranasale, orale, intravaginale) pourraient représenter une approche pertinente pour l'obtention de réponses muqueuses antitumorales [30,31].…”

Section: Vaccins Antitumorauxunclassified