MELANOMA: Two noteworthy biomarker studies identified assessment of T cell infiltrate and clonality as a predictor of subsequent metastasis in early stage disease.

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March 9, 2020

SCIENTIFIC

Two noteworthy biomarker studies identified assessment of T cell infiltrate and clonality as a predictor of subsequent metastasis in early stage disease, and early changes in T cell subsets and clonality as a predictor of response to immunotherapy in advanced disease.

Molecular analysis of primary melanoma T cells identifies patients at risk for metastatic recurrence

Abstract

Primary melanomas >1 mm thickness are potentially curable by resection, but can recur metastatically. We assessed the prognostic value of the T-cell fraction (TCFr) and repertoire T-cell clonality, measured by high-throughput sequencing of the T-cell receptor β-chain in T2–T4 primary melanomas (n = 199). TCFr accurately predicted progression-free survival and was independent of thickness, ulceration, mitotic rate and age. TCFr was second only to tumor thickness in its predictive value, using a gradient-boosted model. For accurate progression-free survival prediction, adding TCFr to tumor thickness was superior to adding any other histopathological variable. Furthermore, a TCFr >20% was protective regardless of tumor ulceration status, mitotic rate or presence of nodal disease. TCFr is a quantitative molecular assessment that predicts metastatic recurrence in primary melanoma patients whose disease has been resected surgically. The present study suggests that a successful T-cell-mediated, antitumour response can be present in primary melanomas.

https://www.nature.com/articles/s43018-019-0019-5

Immune awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy

Abstract

Abstract Our understanding of how checkpoint inhibitors (CPIs) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here, we analyzed peripheral T cell populations after one cycle of CPI treatment and identified a dynamic awakening of the immune system, as revealed by T cell evolution in response to treatment. We sequenced T cell receptors in plasma cell-free DNA and peripheral blood mononuclear cells and performed phenotypic analysis of peripheral T cell subsets from patients with metastatic melanoma treated with CPIs. We found that early peripheral T cell turnover and T cell receptor repertoire dynamics identified which patients would respond to treatment. Additionally, the expansion of a subset of immune effector peripheral T cells we call TIE cells correlated with response. These events are prognostic and occur within 3 weeks of starting immunotherapy, raising the potential for monitoring patients’ responses by using minimally invasive liquid biopsies.

https://www.nature.com/articles/s43018-019-0022-x