TGF-β suppresses type 2 immunity to cancer. Academic Article uri icon

Overview

abstract

  • The immune system uses two distinct defence strategies against infections: microbe-directed pathogen destruction characterized by type 1 immunity1, and host-directed pathogen containment exemplified by type 2 immunity in induction of tissue repair2. Similar to infectious diseases, cancer progresses with self-propagating cancer cells inflicting host-tissue damage. The immunological mechanisms of cancer cell destruction are well defined3-5, but whether immune-mediated cancer cell containment can be induced remains poorly understood. Here we show that depletion of transforming growth factor-β receptor 2 (TGFBR2) in CD4+ T cells, but not CD8+ T cells, halts cancer progression as a result of tissue healing and remodelling of the blood vasculature, causing cancer cell hypoxia and death in distant avascular regions. Notably, the host-directed protective response is dependent on the T helper 2 cytokine interleukin-4 (IL-4), but not the T helper 1 cytokine interferon-γ (IFN-γ). Thus, type 2 immunity can be mobilized as an effective tissue-level defence mechanism against cancer.

publication date

  • October 21, 2020

Research

keywords

  • Neoplasms
  • Signal Transduction
  • Th2 Cells
  • Transforming Growth Factor beta

Identity

PubMed Central ID

  • PMC8347705

Scopus Document Identifier

  • 85093070338

Digital Object Identifier (DOI)

  • 10.1172/JCI76431

PubMed ID

  • 33087928

Additional Document Info

volume

  • 587

issue

  • 7832