Interim Progress: The central hypothesis of this proposal is that PARP inhibition reverses
immunosuppression associated with PTEN-deficient prostate cancer and reprograms the tumor
immune microenvironment to enhance anti-cancer responses to immune checkpoint blockade. To
test this hypothesis, we utilized a bioinformatics approach to profile human primary and
metastatic prostate cancers for non-T cell inflamed vs T cell inflamed gene signatures, and
correlated with common genomic alterations known to drive the malignant phenotype. Critically,
we discovered that prostate cancers harbor mutually exclusive genomic alterations that are
associated with T cell exclusion from the tumor microenvironment. Furthermore, we have made
progress on elucidating the role of PARP inhibitors in reprogramming the immune
microenvironment to sensitize murine PTEN-deficient prostate cancer to PD-1 blockade. Based
on the insight obtained from the computational and preclinical aims described above, we have
received drug and funding approval for an investigator-initiated clinical trial evaluating rucaparib
(PARP inhibitor) in combination with nivolumab (PD-1 blockade) in mCRPC and metastatic
endometrial cancer patients. The trial will begin accrual by April 2018, and we anticipate that
these studies will not only provide a deeper understanding of the impact of PARP inhibition on
activation of anti-cancer immunity, but lead to the development of novel immune-based
combination therapies.

Publications since receiving the award:
(1) Lay Press:
• 2016 Onclive “Top Stories in Oncology” exclusive Q&A interview for press release
on “Evolution of Immunotherapy in Prostate Cancer”
• 2017 Press Releases featured in multiple websites on Prostate Cancer Foundation
Challenge Award
• 2017 Q&A interview on Prostate Cancer Challenge Award, University of Chicago
Comprehensive Cancer Center
• 2017 Press Releases published in Science Life and other websites “By boosting innate
immunity, researchers eradicate aggressive cancer in mice”

(2) Peer-Reviewed:
• Patnaik A, Swanson KD, Csizmadia E, Solanki A, Landon-Brace N, Gehring M,
Helenius K, Olson BM, Pyzer AR, Wang LC, Elemento O, Novak J,Thornley TB,
Asara JM, Montaser L, Timmons JJ, MorganTM, Wang Y, Levantini E, Clohessy JG,
Kelly K, Pandolfi PP, Rosenblatt JM, Avigan DE, Ye H, Karp JM, Signoretti S,Balk
SP and Cantley LC. Cabozantinib eradicates advanced murine prostate cancer by
activating anti-tumor innate immunity. Cancer Discovery 2017; (7): 750-765; PMID:
28274958.
• Sturey B, Patnaik A. Neutrophils and Anti-cancer Immunity: A Paradigm Shift in
Cancer Immunotherapy. Oncoscience 2017; 4(11-12):164-165. PMID: 29344550.
• Li Y, Malapati S, Lin Y, Patnaik A. Challenges with sequencing therapies in
metastatic castrate-resistant prostate cancer. American Journal of
Hematology/Oncology 2017; 13 (12): 26-31.
• Olson B, Liu E, Patnaik A. Co-clinical trials of Novel Immuno-Oncology
combination therapies in mouse models of cancer. Cancer Discovery 2018; Revised
manuscript submitted

Grants Awarded since receiving this award
1. University of Chicago/Northwestern University Prostate SPORE Career Enhancement
Program Award.
2. Bristol-Myers Squibb-funded International Immuno-Oncology Network Research Award.
3. American Cancer Society Institutional Research Grant Award
4. Prostate Cancer Foundation Challenge Award
5. Phi Beta Psi Charity Trust Research Organization

Invited Lectures/Oral Presentations made since receiving the award
International

2017 Invited Speaker, Advanced Centre for Treatment, Research and Education in
Cancer, Tata Memorial Hospital, Mumbai, India
2017 Invited Speaker, National Institute of Immunology, New Delhi, India
2017 Invited Speaker, Post-Graduate Institute for Medical Education and Research,
Chandigarh, India
2017 Invited Speaker, Cancer Immunotherapy Summit, Roche, Madrid, Spain
2017 Oral Presentation “From Cancer Biology to the Clinic”, International
Conference sponsored by European Association for Cancer Research, American Association for Cancer Research-Italian Cancer Society, Florence, Italy
2017 Invited Speaker, Fifth Obai Siddiqi Memorial Oration, National Institute
of Biomedical Sciences, Kalyani, India

National
2016 OncLive State of Science Summit in Prostate Cancer, Chicago, IL
2017 Oral presentation, 10th Annual Prostate Cancer Program Retreat, Fort Lauderdale, FL
2017 Invited speaker, Department of Immunology, Stanford University, Palo Alto, CA
2017 Invited speaker, Bristol-Myers Squibb Discovery Group, Redwood City, CA
2017 Oral presentation, Prostate Cancer Clinical Trials Consortium
2017 Invited speaker, Clovis Oncology

Regional
2017 Invited Speaker, Immunology Program, University of Chicago Comprehensive
Cancer Center, Chicago, IL
2017 Invited Speaker, University of Chicago Developmental Therapeutics
Symposium, Chicago, IL
2017 Invited Speaker, Northwestern/University of Chicago Prostate SPORE, Chicago, IL
2017 Invited Speaker, Hematology/Oncology bimonthly seminar series, University of
Chicago, Chicago, IL
2017 Oral Presentation, Biomedical Clusters All Stars Course, University of Chicago, Chicago, IL
2017 Invited Speaker, Northwestern/University of Chicago External Advisory Board Meeting
2017 Invited Speaker, Hematology/Oncology Research Seminar Series, University of
Chicago, Chicago, IL
2017 Invited Speaker, Biomedical Sciences Cluster Retreat, Lake Geneva, WI