Pancreatic Cancer: Vaccine-Based Therapy May Make Tumors More Susceptible To Treatment

Lei Zheng, M.D., Ph.D. Assistant Professor of Oncology and Surgery Gastrointestinal Cancer Program Division of Immunology The Sidney Kimmel Comprehensive Cancer Center and Department of Oncology Johns Hopkins University School of Medicine The Bunting-Blaustein Cancer Research Building (CRB1) Baltimore, MD 21231MedicalResearch.com Interview with:
Lei Zheng, M.D., Ph.D.
Assistant Professor of Oncology and Surgery
Gastrointestinal Cancer Program
Division of Immunology
The Sidney Kimmel Comprehensive Cancer Center and
Department of Oncology
Johns Hopkins University School of Medicine
The Bunting-Blaustein Cancer Research Building (CRB1)
Baltimore, MD 21231

MedicalResearch: What are the main findings of the study?

Dr. Zheng: This study shows for the first time that treatment with a vaccine-based immunotherapy directly re-programs the pancreatic cancer microenvironment, allowing the formation of lymphoid aggregates, which are organized, lymph node-like, functional immune structures and which convert an immunologically quiescent tumor into an immunologically active tumor. 

MedicalResearch: Were any of the findings unexpected?

Dr. Zheng: The above described lymphoid aggregates were not observed or reported in pancreatic tumors from patients who were not treated by the vaccine.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Zheng: Many malignancies including pancreatic cancer may not be “non-immunogenic” tumors as we have thought.  This misconcept may have drastically slowed the development and application of immune-based therapies for these cancers. Vaccine based immunotherapy may reprogram these cancers, by converting them from a “non-immunogenic” tumor, into an “immunogenic” tumor.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Dr. Zheng: Our study demonstrates that the formation of these immune regulatory structures within pancreatic tumors is the first step toward establishing optimal anticancer immune responses within pancreatic tumors since these lymphoid aggregates can express both activating (“good”) and inhibitory (“bad”) immune signatures.  These data support combination immunotherapies that include both vaccines that induce T cells and facilitate T cell trafficking into the tumors given together with the treatments that boost the “good” immune regulatory signals or block the “bad” immune regulatory signals.   Thus, our study has suggested a new model for developing more effective immunotherapy for traditionally “non-immunogenic” tumors like pancreatic cancer.   One of future researches is to investigate the combinational immunotherapies that include both cancer vaccines and the treatments that boost the “good” immune regulatory signals or block the “bad” immune regulatory signals such as PD-1.

Citation:

Immunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation
Eric R. Lutz, Annie A. Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, Alvin Dorman, Anthony Wamwea, Allison Yager, Daniel Laheru, Christopher L. Wolfgang, Jiang Wang, Ralph H. Hruban, Robert A. Anders, Elizabeth M. Jaffee, and Lei Zheng

Cancer Immunol Res Published OnlineFirst June 18, 2014; doi:10.1158/2326-6066.CIR-14-0027