Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets

Roux, Diana Tronik‐Le; Sautreuil, Mathilde; Bentriou, Mahmoud; Verine, Jérôme; Palma, María Belén; Daouya, Marina; Bouhidel, Fatiha; Lemler, Sarah; LeMaoult, Joël; Desgrandchamps, François; Cournède, Paul-Henry; Carosella, Edgardo D.

doi:10.1007/s00262-020-02530-x

Cited by 24 publications

(18 citation statements)

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“…Also, its expression is associated with inhibited CD8 + T cell activation ( 73 ). Consistent with this, another study has highlighted upregulated gene expression of VISTA in clear cell renal cell carcinoma cells ( 74 ). In clear cell renal cell carcinoma, VISTA is mainly upregulated in CD14 + HLA-DR + macrophages, and its blockade has been associated with decreased tumor growth ( 73 ).…”

Section: The Role Of Vista In the Different Cancerssupporting

confidence: 66%

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

et al. 2021

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Immune checkpoints (ICs) have pivotal roles in regulating immune responses. The inhibitory ICs in the tumor microenvironment (TME) have been implicated in the immune evasion of tumoral cells. Therefore, identifying and targeting these inhibitory ICs might be critical for eliminating tumoral cells. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory IC that is expressed on myeloid cells, lymphoid cells, and tumoral cells; therefore, VISTA can substantially regulate innate and adaptive anti-tumoral immune responses. Besides, growing evidence indicates that VISTA blockade can enhance the sensitivity of tumoral cells to conventional IC-based immunotherapy, e.g., cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. In this regard, the current study aimed to review the current evidence about the structure and expression pattern of VISTA, its role in TME, the clinicopathological significance of VISTA, and its prognostic values in various cancers. Besides, this review intended to collect the lessons from the recent pre-clinical and clinical studies and propose a strategy to overcome tumor immune-resistance states.

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Section: The Role Of Vista In the Different Cancerssupporting

confidence: 66%

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

et al. 2021

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“…TNFRSF9 and its ligand, TNFSF9, were overexpressed in ccRCC, compared with adjacent non-tumor tissues, which were thought to be emerging therapeutic targets. 37 As a co-stimulatory receptor, combination therapy comprised agonist monoclonal antibody targeting TNFRSF9 and CAR-T cells containing TNFRSF9 domain have been explored for therapy of ccRCC in animal models. 38 , 39 Results indicated that the treatment response required CD8 + T cells, which implied the significance of TNFRSF9 + CD8 + T cells in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating TNFRSF9 ⁺ CD8 ⁺ T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response

Wang

Jiang

et al. 2020

OncoImmunology

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“…HLA-G loss of expression at the tumor cell-surface during cell culture could be explained by (i) the absence of transcription factors related to the hypoxic microenvironment or (ii) the lack of several cytokines such as IFN-γ, IFN-α, and IL-10 ( 110 ), but (iii) could also be related to a HLA-G isoform switch that could not be detected since antibodies detecting all the isoforms of HLA-G are missing, particularly for those that lack the α1 domain ( 111 ). Recently, a heterogeneous expression of immune checkpoints including PD-L1, B7H3, ILT2, and HLA-G in RCC was reported ( 112 ). This intratumor heterogeneity was found both at tumor cell and infiltrating immune cell levels in primary RCC ( 113 ).…”

Section: Hla-g Neo-expression In Solid Tumorsmentioning

confidence: 99%

HLA-G Neo-Expression on Tumors

et al. 2020

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HLA-G is known to modulate the immune system activity in tissues where physiological immune-tolerance is necessary (i.e., maternal-fetal interface, thymus, and cornea). However, the frequent neo-expression of HLA-G in many cancer types has been previously and extensively described and is correlated with a bad prognosis. Despite being an MHC class I molecule, HLA-G is highly present in tumor context and shows unique characteristics of tissue restriction of a Tumor Associated Antigen (TAA), and potent immunosuppressive activity of an Immune CheckPoint (ICP). Consequently, HLA-G appears to be an excellent molecular target for immunotherapy. Although the relevance of HLA-G in cancer incidence and development has been proven in numerous tumors, its neo-expression pattern is still difficult to determine. Indeed, the estimation of HLA-G's actual expression in tumor tissue is limited, particularly concerning the presence and percentage of the new non-canonical isoforms, for which detection antibodies are scarce or inexistent. Here, we summarize the current knowledge about HLA-G neo-expression and implication in various tumor types, pointing out the need for the development of new tools to analyze in-depth the HLA-G neo-expression patterns, opening the way for the generation of new monoclonal antibodies and cell-based immunotherapies.

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Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets

Cited by 24 publications

References 40 publications

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

Tumor-infiltrating TNFRSF9 ⁺ CD8 ⁺ T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response

HLA-G Neo-Expression on Tumors

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Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets

Cited by 24 publications

References 40 publications

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

Tumor-infiltrating TNFRSF9 + CD8 + T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response

HLA-G Neo-Expression on Tumors

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Tumor-infiltrating TNFRSF9 ⁺ CD8 ⁺ T cells define different subsets of clear cell renal cell carcinoma with prognosis and immunotherapeutic response