Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells

TLDR

Spontaneous T‑cell priming frequently occurs in response to growing tumors, yet many models fail to achieve tumor control. The study aimed to identify the innate immune mechanisms that drive natural antitumor T‑cell responses. In human metastatic melanoma, a type I interferon transcriptional signature correlated with T‑cell markers, and in mice IFN‑β produced by CD11c⁺ cells was essential for tumor‑induced T‑cell priming; IFN signaling in hematopoietic cells—particularly CD8α⁺ dendritic cells—was required for their intratumoral accumulation and for effective antitumor immunity.

Abstract

Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c+ cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α+ dendritic cells, which were demonstrated to be essential using Batf3−/− mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α+ DCs.