TAMs expressing TREM2 are a potential therapeutic target (from Fig. 2F of Cao et al., Cancer Immunol Res 2019)
Understanding the mechanisms underlying resistance to anti–PD-1 therapy is key to developing new therapeutics. Binnewies et al. find that human and mouse immunosuppressive tumor-associated macrophages (TAM) express triggering receptor expressed on myeloid cells 2 (TREM2) and that the presence of these cells in the tumor microenvironment correlates with an exhausted T-cell state in human tumors and anti–PD-1 resistance in mouse models of cancer. A TREM2-specific antibody promotes antitumor immunity in mice by depleting TAMs, leading to enhanced CD8+ T-cell function. It also reverses anti–PD-1 resistance, highlighting the potential of targeting TREM2 to treat patients with anti–PD-1–resistant tumors.
Binnewies M, …, Sriram V. Cell Rep 2021 Oct 19;37:109844.
Loss of antigen can have an impact on therapy efficacy (by Silverisdead via Flickr)
Tumor loss of target antigen(s) can lead to resistance...
