Thomas Urban Marron, M.D., Ph.D., CLIP Investigator Icahn School of Medicine at Mount Sinai

Checkpoint immunotherapies targeting the PD-1/PD-L1 pathway have transformed how we treat several types of advanced cancers, and in some cases—like metastatic lung cancer—they’ve been found to be even more effective when combined with traditional chemotherapy, appearing to have synergistic effects. Emerging studies demonstrate that this combination may be even more effective in the neoadjuvant (pre-surgical) setting for patients who will have their tumors resected. While immunotherapy has revolutionized the field of oncology, the majority of patients with metastatic cancer still do not significantly benefit from checkpoint immunotherapy, even in combination with chemotherapy. There is a significant need for more in depth analysis of the effects of immunotherapies alone and in combination with chemotherapy so as to (1) identify biomarkers to predict who will respond to therapy, so as to avoid giving futile therapies to patients whom will not benefit and (2) identify the most rational approach to combining new immunotherapies with “classical” chemotherapy as well as emerging immune and targeted therapies.

Dr. Thomas Marron and his team have designed a “window-of-opportunity” trial in which lung cancer patients are treated with PD-1 immunotherapy, with or without chemotherapy, prior to surgery. In this trial, patients’ tumors, blood, and stool will be examined both before and after treatment in order to characterize the response to therapy in depth and address critical questions about the mechanism underlying cancer immunotherapy. Using new platforms developed by Dr. Marron’s collaborators they will investigate dynamic changes at the cellular level (monitoring ability of the treatment to disrupt anti-immune architecture in many tumors, and allow penetration of anti-tumor immune cells such as T cells) and at the single-cell proteomic and genomic levels (a deep dive into each individual immune cell within the tumor and neighboring tissue to understand potential barriers to tumor eradication). Correlation of these changes with patient outcome will aid in designing iterative trials for both patients whose tumors can be resected and those with metastatic disease.

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