Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Becht, Étienne; Giraldo, Nicolás A.; Germain, Claire; Reyniès, Aurélien de; Laurent‐Puig, Pierre; Zucman‐Rossi, Jessica; Dieu-Nosjean, Marie-Caroline; Fridman, Wolf‐Herman

doi:10.1016/bs.ai.2015.12.002

Cited by 177 publications

(158 citation statements)

References 543 publications

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“…The above data supports the concept that immunotherapeutic interventions can be designed by mapping the mutational and immune landscape of human cancers (38,39). In order to provide stronger evidence that the tumor mutanome can be used as a potential biomarker of clinical benefit in cancer immunotherapies, either alone or in combination with immune landscape signatures, analyses of larger cohorts of patients are required.…”

Section: The Prognostic and Predictive Value Of The Mutational Load Isupporting

confidence: 60%

Neoantigen-based cancer immunotherapy

Bobisse¹,

Foukas²,

Coukos³

et al. 2016

Ann. Transl. Med.

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Emerging clinical evidence on the role of the antitumor activity of the immune system has generated great interest in immunotherapy in all cancer types. Recent clinical data clearly demonstrated that human tumor cells express antigenic peptides (epitopes) that can be recognized by autologous tumor-specific T cells and that enhancement of such immune reactivity can potentially lead to cancer control and cancer regression in patients with advanced disease. However, in most cases, it is unclear which tumor antigens (Ags) mediated cancer regression.Mounting evidence indicates that numerous endogenous mutated cancer proteins, a hallmark of tumor cells, can be processed into peptides and presented on the surface of tumor cells, leading to their immune recognition in vivo as "non-self" or foreign. Massively parallel sequencing has now overcome the challenge of rapidly identifying the comprehensive mutational spectrum of individual tumors (i.e., the "mutanome") and current technologies, as well as computational tools, have emerged that allow the identification of private epitopes derived from their mutanome and called neoantigens (neoAgs). On this basis, both CD4 + and CD8 + neoantigen-specific T cells have been identified in multiple human cancers and shown to be associated with a favorable clinical outcome.Notably, emerging data also indicate that neoantigen recognition represents a major factor in the activity of clinical immunotherapies. In the post-genome era, the mutanome holds promise as a long-awaited 'gold mine' for the discovery of unique cancer cell targets, which are exclusively tumor-specific and unlikely to drive immune tolerance, hence offering the chance for highly promising clinical programs of cancer immunotherapy.

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Section: The Prognostic and Predictive Value Of The Mutational Load Isupporting

confidence: 60%

Neoantigen-based cancer immunotherapy

Bobisse¹,

Foukas²,

Coukos³

et al. 2016

Ann. Transl. Med.

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“…A T cell-rich micromilieu seems a favorable prognostic marker in tumors, depending on the immune contexture (39,40). In cutaneous melanoma, the prognostic value of tumor infiltrating lymphocytes in the primary tumor, as well as lymph node metastases, has been suggested 20 years ago (41,42) and has recently been confirmed and expanded (43)(44)(45).…”

Section: Distribution and Intensity Of Tumor Infiltrating T Cellsmentioning

confidence: 98%

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

Groß¹,

Erdmann²,

Haendle³

et al. 2017

JCI Insight

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“…In addition, the costimulatory molecules were upregulated. Thus, the infiltration of OPSCC by HPV16-specific Th1/Th17 cells is associated with the presence of a highly active tumor microenvironment consisting of a dense type I-oriented immune cell infiltrate, known to favor immune-mediated control of cancer cells (29). …”

Section: Tumor Infiltration By Hpv-specific T Cells Correlates With Hmentioning

confidence: 99%

Intratumoral HPV16-Specific T Cells Constitute a Type I–Oriented Tumor Microenvironment to Improve Survival in HPV16-Driven Oropharyngeal Cancer

Welters

Santegoets

et al. 2018

Clinical Cancer Research

143

193

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Purpose: Human papillomavirus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) has a much better prognosis than HPV-negative OPSCC, and this is linked to dense tumor immune infiltration. As the viral antigens may trigger potent immunity, we studied the relationship between the presence of intratumoral HPV-specific T-cell responses, the immune contexture in the tumor microenvironment, and clinical outcome.Experimental Design: To this purpose, an in-depth analysis of tumor-infiltrating immune cells in a prospective cohort of 97 patients with HPV16-positive and HPV16-negative OPSCC was performed using functional T-cell assays, mass cytometry (CyTOF), flow cytometry, and fluorescent immunostaining of tumor tissues. Key findings were validated in a cohort of 75 patients with HPV16-positive OPSCC present in the publicly available The Cancer Genome Atlas database.Results: In 64% of the HPV16-positive tumors, type I HPV16-specific T cells were present. Their presence was not only strongly related to a better overall survival, a smaller tumor size, and less lymph node metastases but also to a type I-oriented tumor microenvironment, including high numbers of activated CD161 þ T cells, CD103 þ tissue-resident T cells, dendritic cells (DC), and DC-like macrophages. Conclusions:The viral antigens trigger a tumor-specific T-cell response that shapes a favorable immune contexture for the response to standard therapy. Hence, reinforcement of HPV16-specific T-cell reactivity is expected to boost this process. Clin Cancer Res; 24(3); 634-47. Ó2017 AACR.

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Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Cited by 177 publications

References 543 publications

Neoantigen-based cancer immunotherapy

Neoantigen-based cancer immunotherapy

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

Intratumoral HPV16-Specific T Cells Constitute a Type I–Oriented Tumor Microenvironment to Improve Survival in HPV16-Driven Oropharyngeal Cancer

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