Background: Many types of cancer recruit neutrophils that could have pro-tumor or antitumor effects on tumor development. Numerous findings in murine models suggest a predominantly pro-tumor 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 anti-tumor mechanisms are activated. To date, the majority of experimental approaches to study neutrophils in cancer patients have been limited to the examination of circulating blood neutrophils. The phenotype and function of tumor-associated neutrophils (TANs) in humans, particularly in the early stages of tumor development, have not been extensively investigated. Thus, the long-term goal of our work is to characterize human TANs and determine their specific role in tumor development. I will describe the phenotypes of different TAN subsets that we have identified in early stage lung tumors, as well as their functional dialog with T cells. Understanding the role of TANs in regulating T cell responses is particularly important because cytotoxic T lymphocytes are the primary effector cells mediating antigen-driven anti-tumor immunity. Briefly, my team provides the first evidence of two subsets of TANs in lung cancer. All TANs had an activated phenotype and could support (rather than inhibit) T cell functions to some degree in early stage lung cancer patients. However, they attenuated this ability in large-sized tumors. We have identified a subset of TAN in early-stage lung tumors that can undergo a unique differentiation process resulting in formation of specialized subset of APC-like hybrid neutrophils. These hybrid TANs had enhanced ability to trigger and support T cell responses in direct cell-cell interactions. In addition we found that hybrid neutrophils could be ideal powerful effector cells for antibody-mediated immunotherapy of cancer. These properties of hybrid and canonical neutrophils open new perspectives to boost the efficacy of current immunotherapy.

Selected publications:

1. Singhal S, … and Eruslanov E. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features in Early-Stage Human Lung Cancer., Cancer Cell (2016)

2. Eruslanov E. et al. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer., JCI (2014)

3. Eruslanov E. et al. Mouse versus Human Neutrophils in Cancer: A Major Knowledge Gap., Trends in Cancer (2017)