Summary authored by Kohsuke Isomoto, MD, PhD

Bedside to Bench: Investigating Response & Resistance Mechanisms to Immune Checkpoint Therapy

Kohsuke Isomoto, MD, PhD

Dr. Sharma delivered an insightful overview of immune checkpoint blockade therapy and elucidated the vital process for translational researchers like us on harnessing clinical data for research and reciprocating the benefits to the patients:

1. Reverse Translation from Bedside to Bench: Emphasizing the essence of the iterative process, Dr. Sharma spotlighted the continuous cycle of gathering patient data in the clinic, dissecting it in the lab, and subsequently channeling the research outcomes back to the patients. She enriched her explanation with personal experiences for enhanced clarity.

2. Foundational Comprehension of Immunity: Venturing into immunotherapy research mandates a robust foundational grasp of immunity. Dr. Sharma provided a snapshot of the mechanism of action of PD-1 and CTLA-4 antibodies. The intricate understanding of this mechanism, which served as the bedrock for the invention of anti-CTLA-4 and anti-PD-1 antibodies, was accentuated.

3. Checkpoint Inhibitors’ Influence on the Tumor Microenvironment & The Multifaceted Nature of Immunotherapy: Evaluating therapeutic impacts isn’t confined to just pre-treatment samples. Dr. Sharma stressed the significance of examining both pre- and post-treatment samples to capture the full spectrum of the immune response. Through a comparative analysis of samples taken before and after Immune Checkpoint Inhibitors (ICI) treatment, it was evidenced that immunotherapy prompts the influx of activated T-cells into tumors. She further discerned compensatory pathways governing these phenomena, which paved the way for novel therapeutic targets.

4. Teamwork’s Pivotal Role: The landscape of cancer treatment is evolving, with immune checkpoint inhibitor therapies now being synergized with surgeries, radiation, and varied chemotherapies. Orchestrating such intricate research demands a concerted effort from a multidisciplinary team of experts.

In her closing comments, Dr. Sharma highlighted the potential of tissue-based clinical trials, like Neoadjuvant therapies designed for specific patient cohorts. These studies not only demonstrate practicality but also present a unique opportunity to gauge the preliminary effects of treatments on cancer and their biological outcomes.