NR2F6 intrinsic role in anti-tumor NK cell responses

The focus of cancer immunotherapy primarily lies on the adaptive, targeted immune response, where CD8- and CD4-positive T-lymphocytes play a central role due to their ability to respond specifically to antigens. However, increasing attention is being directed toward natural killer (NK) cells, which are part of the innate immune system, in tumor control. NK cells provide a rapid and natural defense against altered self-cells, serving as a critical first line of defense in combating infectious diseases and cancer. Moreover, NK cells can inhibit the spread of cancer cells from the primary tumor to other organs, thereby limiting metastasis. Nevertheless, NK cells often lose their effectiveness once they infiltrate a tumor. We have identified a key molecule that suppresses NK cell activity in tumor defense. The biological function of this hormone receptor in NK cells remains unclear. Preliminary results from preclinical mouse models, however, suggest that it plays an essential role in tumor rejection. Animals lacking this hormone receptor exhibit significantly more efficient NK cell-dependent rejection of tumors and lung metastases compared to control animals. Our research project aims to investigate in detail how the targeted loss of the hormone receptor in NK cells affects their development and function. In the next phase, we intend to analyze the anti-tumor activity of NK cells during tumor growth and metastasis in the presence and absence of immune checkpoint inhibition. As a critical translational step, this hormone receptor will ultimately be knocked out in the human NK-92 cell line as well as in primary human NK cells to study the functional effects during tumor growth in both tissue cultures and immunodeficient mice. We hope that future immunotherapies targeting the suppression of this hormone receptor`s function in NK cells will present an effective strategy to prevent tumor growth and metastasis.