Mouse versus Human Neutrophils in Cancer: A Major Knowledge Gap

Our current understanding of the role of neutrophils in tumor development has greatly depended on murine models of cancer. Uncertainty exists regarding the phenotypes, functional roles, and relationships between different granulocytic cell populations during tumor progression. The protumoral role of neutrophils in cancer development in mice is mostly associated with the idea of the development of PMN-MDSC. The fundamental differences between mice and humans in the evolution of tumors, immune and inflammatory responses, genetic diversity, and intrinsic biology of neutrophils might have a profound impact on the function of neutrophils. The detailed functions of tumor-associated neutrophils in human cancers remain to be determined. Many types of cancer recruit neutrophils that could have protumor or antitumor effects on tumor development. Numerous findings in murine models suggest a predominantly protumoral role for neutrophils in cancer development. However, there are fundamental differences between mouse and human tumors in the evolution of tumors, genetic diversity, immune response, and also in the intrinsic biology of neutrophils that might have a profound impact on tumor development and the function of these cells. A crucial difference is that the majority of mouse tumor models lack the prolonged initial phases of multistage tumor evolution present in humans when antitumoral mechanisms are activated. In this review, we discuss the challenges specific to cross-species extrapolation of neutrophil function during mouse versus human tumor development. Many types of cancer recruit neutrophils that could have protumor or antitumor effects on tumor development. Numerous findings in murine models suggest a predominantly protumoral role for neutrophils in cancer development. However, there are fundamental differences between mouse and human tumors in the evolution of tumors, genetic diversity, immune response, and also in the intrinsic biology of neutrophils that might have a profound impact on tumor development and the function of these cells. A crucial difference is that the majority of mouse tumor models lack the prolonged initial phases of multistage tumor evolution present in humans when antitumoral mechanisms are activated. In this review, we discuss the challenges specific to cross-species extrapolation of neutrophil function during mouse versus human tumor development.