Influence of human immune cells on cancer: studies at the University of Colorado

Abstract

There will be over half a million cancer-related deaths in the United States in 2012, with lung cancer being the leader followed by prostate in men and breast in women. There is estimated to be more than one and a half million new cases of cancer in 2012, making the development of effective therapies a high priority. As tumor immunologists, we are interested in the development of immunotherapies because the immune response offers exquisite specificity and the potential to target tumor cells without harming normal cells. In this review, we highlight the current advances in the field of immunotherapy and the current work being completed by laboratories at University of Colorado School of Medicine in multiple malignancies, including breast cancer, lung cancer, melanoma, thyroid cancer, and glioblastoma. This work focuses on augmenting the anti-tumor response of CD8 T cells in the blood, lymph nodes, and tumors of patients, determining biomarkers for patients who are more likely to respond to immunotherapy, and identifying additional anti-tumor and immunosuppressive cells that influence the overall response to tumors. These collaborative efforts will identify mechanisms to improve immune function, which may elucidate therapeutic targets for clinical trials to improve patient health and survival.

Fig. 1

Breast cancer CD8 TILs proliferate (Ki-67) and produce IFN-γ in response to TCR stimulation. CD8 T cells were isolated from total PBMC post-Ficoll separation (left). CD8 TILs were isolated according to the protocol in Fig. 2 (right). Cells were stimulated postselection for 5 days with αCD3αCD28. On day five, the cells were restimulated with PMA, ionomycin, and brefeldin-A for 6 h, stained intracellularly for Ki-67 and IFN-γ, and analyzed by flow cytometry

Fig. 2

TIL isolation protocol