The goal of my laboratory is to elucidate the molecular mechanisms that limit renal cell carcinoma patient responses to immunotherapy. The laboratory’s translational studies are concentrated on enhancing anti-tumor immunity through improved myeloid cell function and cytolytic T cell activity within renal cell carcinoma. Our laboratory’s findings from a pilot trial in metastatic renal cell carcinoma combining high-dose radiation of kidney tumors with surgical resection, provide a glimpse into the immune activating effects of radiation in human cancer. The laboratory’s most recent studies performed in collaboration with Dr. Scott Abrams shed light on the role key transcription factors at play in macrophage behavior and patient outcome.
Muhitch JB, Hoffend NC, Azabdaftari G, Miller A, Bshara W, Morrison CD, Schwaab T, Abrams SO. Tumor-associated macrophage expression of interferon regulatory Factor-8 (IRF8) is a predictor of progression and patient survival in renal cell carcinoma. J Immunther Cancer. 2019; 7: 155.
Singh AK, Winslow T, Habiby Kermany M, Goritz V, Heit L, Miller A, Hoffend NC, Stein LC, Kumaraswamy LK, Warren GW, Bshara W, Odunsi KO, Matsuzaki J, Abrams SI, Schwaab T, Muhitch JB. A pilot study of stereotactic body radiation therapy combined with cytoreductive nephrectomy for metastatic renal cell carcinoma. Clin Cancer Res. 2017; 23: 5055-5065.
Ku A, Muhitch JB, Diehl M, Abrams SI, Ostrand-Rosenberg S, Evans SS. Myeloid-derived suppressor cell-mediated downregulation of L-selectin limits T cell trafficking in lymph nodes which can be alleviated by systemic thermal therapy. eLife. 2016; 5:e17375.
Battaglia S and Muhitch JB. Unmasking targets of antitumor immunity via high-throughput antigen profiling. Curr Opin Biotechnol. 2016; 42: 92-97.
Fisher D, Muhitch JB, Kim M, Doyen K, Bogner P, Evans SS, Skitzki J. Intraoperative intravital microscopy permits the study of human tumour vessels. Nat Commun. 2016; 7: 10684.
Mikucki M, Fisher D, Matsuzaki J, Skitzki JJ, Gaulin N, Muhitch JB, Frelinger J, Odunsi K, Gajewski T, Luster A, Evans SS. Non-redundant requirement for CXCR3 signalling during tumoricical T-cell trafficking across tumour vascular checkpoints. Nat Commun. 2015; 6: 7458.
Muhitch JB and Schwaab T. High-dose interleukin-2 (IL-2) for metastatic renal cell carcinoma: can the first anti-tumor immunotherapy be reinvented? Immunotherapy. 2014; Sep 6; (9): 955-958.