Ashleigh R Poh, Christopher G Love, David Chisanga, James H Steer, David Baloyan, Michaël Chopin, Stephen Nutt, Jai Rautela, Nicholas D Huntington, Nima Etemadi, Megan O'Brien, Ryan O'Keefe, Lesley G Ellies, Christophe Macri, Justine D Mintern, Lachlan Whitehead, Gangadhara Gangadhara, Louis Boon, Ashwini L Chand, Clifford A Lowell, Wei Shi, Fiona J Pixley, Matthias Ernst
Although immunotherapy has revolutionized cancer treatment, many immunogenic tumors remain refractory to treatment. This can be largely attributed to an immunologically "cold" tumor microenvironment characterized by an accumulation of immunosuppressive myeloid cells and exclusion of activated T cells. Here, we demonstrate that genetic ablation or therapeutic inhibition of the myeloid-specific hematopoietic cell kinase (HCK) enables activity of antagonistic anti-programmed cell death protein 1 (anti-PD1), anti-CTLA4, or agonistic anti-CD40 immunotherapies in otherwise refractory tumors and augments response in treatment-susceptible tumors...
June 24, 2022: Science Advances