Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis.
作者： Yaqing Zhang , Jenny Lazarus , Nina G. Steele , Wei Yan , Ho-Joon Lee
DOI: 10.1158/2159-8290.CD-19-0958
关键词:
摘要: Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to immunosuppressive microenvironment, we depleted Tregs a model of Contrary our expectations, Treg depletion failed relieve immunosuppression led accelerated tumor progression. We show that key source TGFβ ligands and, accordingly, their reprogramed fibroblast population, with loss tumor-restraining, smooth muscle actin-expressing fibroblasts. Conversely, observed an increase chemokines Ccl3, Ccl6, Ccl8 leading increased myeloid cell recruitment, restoration immune suppression, promotion carcinogenesis, effect was inhibited by blockade common CCL3/6/8 receptor CCR1. Further, unleashed pathologic CD4+ T-cell responses. Our data point new mechanisms regulating differentiation cancer support notion fibroblasts heterogeneous population different opposing functions carcinogenesis. SIGNIFICANCE: Here, describe unexpected cross-talk between resulted inflammatory subsets, turn driving infiltration through CCR1, thus uncovering potentially therapeutic approach cancer.See related commentary Aykut et al., p. 345.This article is highlighted In This Issue feature, 327.
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