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Top Line: Our current immunotherapy paradigm revolves around T-cells.
The Study: Let’s look again at classifying soft tissue sarcoma (STS) according to the immune signature of the tumor microenvironment (TME). There were five distinct TME signatures labeled A to E according to immune gene expression. Classes A and B were immunologically cold, while class C was mainly characterized by vascular gene expression signatures. It was the D and, in particular, E class that exhibited the most intense immune expression. These had the best clinical outcomes and best response to immunotherapy. As this editorial points out, though, that shouldn’t be our biggest focus. While CD8+ T-cell expression and PD-1 expression were expectedly high, it was B-cell gene expression that was the main determinant of E classification, patient survival, and response to immunotherapy. Second was the finding that the B-cell signature was closely linked to the presence of tertiary lymphoid structures, ectopic lymphoid organs that develop outside lymphoid tissues. Tertiary lymphoid structure maturity culminates in the presence of functional germinal centers within tumor tissues. And it's these germinal centers that are the heart of adaptive immunity.
TBL: B-cell gene expression and the formation of tertiary lymphoid structures in the sarcoma microenvironment are strong predictors of prognosis and response to immunotherapy. | Bruno, Nature 2020 and Sautès-Fridman, Nature 2020