STOCKHOLM — Researchers at Karolinska Institutet published findings on neutrophil activity during cancer treatment in the journal Immunity. The study reported that neutrophils can decrease the efficacy of cancer immunotherapy.

Scientists evaluated how neutrophils interact with immunotherapy using mouse models of melanoma and breast cancer. The research team compared mice with standard neutrophil counts to those genetically depleted of neutrophils.

Immunotherapy treatments resulted in greater tumor volume reduction in mice lacking neutrophils. Tumors in mice without neutrophils contained higher quantities of activated T cells. Shengduo Pei, a former doctoral student and study first author, stated, "We see that neutrophils can dampen the effect of immunotherapy by influencing T-cell activity."

Neutrophils alter their cellular expression patterns following immunotherapy administration. After immunotherapy treatment begins, neutrophils start producing the protein PD-L1, which functions as a suppressor of T cell activity. Interferon-gamma released by tumor-resident immune cells triggers this PD-L1 expression in neutrophils. Targeted removal of PD-L1 or the interferon-gamma receptor from neutrophils enhanced immunotherapy results in the study models.

Analysis of human lung cancer patient specimens indicated that similar neutrophil-mediated immune regulation occurs in human tumors. Professor Mikael Karlsson stated, "This means that the neutrophil response to immunotherapy is not static but governed by signals in the tumor environment. It also shows the importance of studying blocking mechanisms that arise once treatment begins. The results may contribute to the development of treatments that combine several therapies to counteract these inhibitory effects."

The study involved collaboration among research institutions in Sweden, the U.S., Germany, and China. The research received funding from the National Institutes of Health, the Swedish Cancer Society, and the Swedish Foundation for Strategic Research.