A variety of immune cells, the most abundant being macrophages and T cells, typically infiltrate tumors. These immune cells can recognize and kill cancer cells. For example, macrophages activated with interferon-gamma and lipopolysaccharide can kill cancer cells both directly and indirectly, by enhancing the cytotoxic T cells' killing activities. Cancer cells, however, evade the attacking immune cells and even re-instruct macrophages and cytotoxic T cells to facilitate tumor growth, rather than halt it. It is now clear that in a clinical setting T cell deactivation can be overcome using anti-CTLA4 or anti-PDL1 antibodies, leading to tumor regression. Although exciting recoveries are experienced by many patients, the majority of patients do not have long-term benefits of such treatments. Therefore, ways are urgently needed to modify these immune activating approaches so they become beneficial to an expanded patient population.
One underexplored strategy, which we are undertaking, is to re-activate the macrophages so they can kill cancer cells and further enhance the anti-tumor T cell responses. To test different strategies for re-activating macrophages, we are developing co-culture models with cancer cells, T cells and macrophages. In addition, we study interactions between these three cell types in vivo, using intravital imaging of mouse models of breast and pancreatic cancer. Our findings will offer new insights into the mechanisms by immune suppressive signals can be overcome and generate new methods for studying immune responses to cancer in real-time.
Citation Format: Ana S. Almeida, Tim Kees, Mikala Egeblad. Modulating innate-adaptive immune cell interactions to achieve tumor rejection. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B62.
- ©2015 American Association for Cancer Research.