T-Cell Repertoire in Combination with T-Cell Density Predicts Clinical Outcomes in Patients with Merkel Cell Carcinoma

Farah, Maya; Reuben, Alexandre; Spassova, Ivelina; Yang, Richard K.; Kubat, Linda; Nagarajan, Priyadharsini; Ning, Jing; Li, Wen; Aung, Phyu P.; Curry, Jonathan L.; Torres‐Cabala, Carlos A.; Hudgens, Courtney W.; Ugurel, Selma; Schadendorf, Dirk; Gumbs, Curtis; Little, Latasha; Futreal, Andrew; Wistuba, Ignacio I.; Prieto, Víctor G.; Wang, Linghua; Wong, Michael K.; Wargo, Jennifer A.; Becker, Jürgen C.; Tetzlaff, Michael T.

doi:10.1016/j.jid.2020.02.031

Cited by 16 publications

(16 citation statements)

References 54 publications

(70 reference statements)

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“…The presence of tumor-infiltrating cytotoxic CD8 + T lymphocytes at MCC sites indicates an active immune response to neoantigens and is associated with an improved outcome [82][83][84]. This concept has been further underlined in a recent study, where T cell receptor (TCR) sequencing was performed and the association between metrics of the TCR repertoire and MCC patient survival was measured [85]. For the examined patients, an association between the abundance of T cell clones, which reflects antigen-driven T cell expansion, and improved outcome was detected.…”

Section: Immunologymentioning

confidence: 99%

“…For the examined patients, an association between the abundance of T cell clones, which reflects antigen-driven T cell expansion, and improved outcome was detected. Moreover, abundance of T cell clones, together with high CD3 + or CD8 + T cell density at the periphery of the primary MCC, constitutes a strong prognostic indicator of better survival in these patients [85].…”

Section: Immunologymentioning

confidence: 99%

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Merkel Cell Carcinoma

et al. 2021

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Merkel cell carcinoma (MCC) is a rare and extremely aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. This review intends to propose a comprehensive evaluation of MCC epidemiology, clinical features, pathogenetic mechanisms, diagnosis, and therapies. A section is dedicated to immunological aspects and another to the involvement of angiogenesis and angiogenic growth factors in MCC progression, proposing novel diagnostic and therapeutic approaches. Advanced MCC tumors have been treated with immune checkpoint inhibitors with effective results. Therefore, the state of art of this immunotherapy is also examined, reporting on the most recent clinical trials in the field. We conclude by underlining the achievements in the understanding of MCC pathology and indicating the present needs for effective diagnosis and therapeutic management of the disease.

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Section: Immunologymentioning

confidence: 99%

Section: Immunologymentioning

confidence: 99%

Merkel Cell Carcinoma

et al. 2021

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“…Many biomarkers have been implicated as potential prognosticators in MCC [ 30 , 31 , 32 , 33 , 34 , 35 ], but the integrity of the host immune system has been argued to be the most significant [ 36 ]. Indeed, antigen-specific T-cells detected in patients demonstrate a reduced expression of CD69 and CD25.…”

Section: Tumor Microenvironment In MCCmentioning

confidence: 99%

“…In recent years, researchers have sought to associate the TCR repertoire with MCC patients’ risk for disease-specific morbidities and how they might respond to specific immunotherapies. Farah et al evaluated the TCR repertoire associated with 72 primary MCCs and correlated metrics of the TCR repertoire with clinicopathologic characteristics and patient outcomes [ 36 ]. They found that higher TCR diversity was associated with fewer metastases, lower stages at presentation, and longer times until first lymph node metastasis [ 36 ].…”

Section: T-cell Receptor Repertoiresmentioning

confidence: 99%

T-Cell Mediated Immunity in Merkel Cell Carcinoma

Ouyang

Zheng

Agak

2022

Cancers

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Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4+, CD8+, and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed.

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“…2. In the article by Farah et al (2020), what was the Simpson's dominance index (SDom) metric used to measure, and how was it related to patient outcomes for MCC?…”

mentioning

confidence: 99%