Cancer Immunology

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CANCER IMMUNOLOGY PROGRAM: SUMMARY The Cancer Immunology (CI) Program at the Hollings Cancer Center (HCC) seeks to uncover how the immune system recognizes and kills tumors and to use this information to develop effective immuno-oncology (IO) strategies to treat patients. Three unifying themes promote these goals: 1) immunotherapy; 2) inflammation and tolerance; and 3) T-cell biology. Notable progress has been made in all three areas. This includes launch and completion of the first phase 1b/2 trial on the treatment of advanced non-small cell lung cancer using the combination of a PD-1 antagonist and super-agonist recombinant IL-15, developing novel oncolytics that block the PD-1 pathway, a first report elucidating how platelets blunt T-cell immunity via the GARP-TGF axis, eluci- dating the roles of CD38 in generating the anti-tumor hybrid Th1/17 cells, uncovering the mechanism that sus- tains cytokine signaling, and discovering highly potent human CD26+ lymphocytes for cell therapy of cancer. The program is co-led by two exceptional immunologists with distinct basic and clinical backgrounds who col- laboratively build a synergistic program conducting cutting edge research: Zihai Li, MD, PhD is a board-certi- fied medical oncologist and immunologist with expertise in inflammation and tolerance; Chrystal Paulos, PhD is a tumor immunologist with expertise in basic T-cell biology and adoptive T-cell transfer therapy. There are 20 program members from seven academic departments. The annual funding base is $4.4 million in direct costs, excluding career development and training grants. There are 28 active cancer-related funded projects, nine from the NCI, including a new multi-institutional program project (NCI P01 CA186866). In the current cycle, CI members published 138 peer-reviewed papers, of which 40% are intra- and 43% interprogrammatic collabora- tions. The exceptional impact of the program’s research is highlighted by 20 publications in journals with an impact factor >10 including Cancer Discov, Cell Metab, Sci Transl Med, J Clin Invest, Nat Med (2018), Nat Commun, Nat Struct Mol Biol, and Lancet Oncol (2018). Since the last renewal, the HCC contributed funding to recruit seven new CI members, including one senior clinician-scientist (Raymond DuBois, MD, PhD). Their re- cruitment fostered new investigator-initiated clinical trials and provided big data analysis expertise. HCC also supported a number of events, including inter-programmatic joint spring symposia and multi-institutional re- treats. The program benefits from all HCC shared resources, particularly the Biostatistics and Flow Cytometry & Cell Sorting Shared Resources, which added a 2nd-generation mass cytometer for high-dimensional single- cell analysis, reflecting a significant institutional investment. With the maturation of the CI Program into a syn- ergistic team of multidisciplinary investigators, the rapid progress of IO, strong support from the new HCC lead- ership, and the key shift in the field toward harnessing the immune system to treat cancer, the CI Program is positioned for robust progress in all thematic research areas in the next funding cycle.