CyTOF analysis of anti-tumor responses

Patients with cancer are increasingly treated by immunotherapy, yet some tumors remain refractory to such therapies. In Cell, Spitzer et al. utilize mass cytometry to perform systems analysis of effective anti-tumor responses in a mouse model of spontaneous triple-negative breast cancer, a tumor type that resists checkpoint blockade directed against the immunoinhibitory receptor PD-1. Effective responses are elicited by intratumoral injection of allogeneic immunoglobulin, antibody to the costimulatory receptor CD40 and interferon-g. Enduring anti-tumor responses require the activation and proliferation of immune cells in both tumor sites and 'systemic' sites, including activation of B cells and CD4⁺ T cells in lymphoid tissues. Surprisingly, a dominant component of this effective response is CD90⁺CD4⁺ T cells rather than CD8⁺ T cells. Patients with melanoma who respond to antibody to the immunomodulatory receptor CTLA-4 likewise have a greater frequency of activated CD4⁺ T cells than that of non-responders. Such findings should inform the design of future clinical trials.

Cell 168, 487–502 (2017)