The immune system protects the body by identifying and eliminating potential threats such as infections, toxins, and cancers, however, many cancers have developed ingenious mechanisms to evade immune surveillance. Historically, advanced cancer treatment has heavily relied on chemotherapies, this treatment has various and sometimes significant side effects. Despite early failures, recent efforts have shown success in reinvigorating an exhausted immune system to target cancer cells with far fewer adverse effects. Although, not all patients benefit from immunotherapy, understanding the reasons for this failure is key to developing the next generation of immunotherapeutics.
In collaboration with Tempus Labs, Dr. Janakiraman Subramanian, Director of Thoracic Oncology and Center for Precision Oncology at Saint Luke’s Cancer Institute performed a large-scale next generation sequencing analysis from de-identified records of lung cancer patients to understand the mechanisms promoting immunotherapy response. Using novel machine learning models, the team analyzed DNA, RNA, and protein data from 2,700 lung cancer samples to measure their neoantigen (proteins unique to cancer cells) load and understand the landscape of tumor-infiltrating immune cells.
Subramanian’s work indicates that tumors sensitive to immunotherapy have a higher expression of neoantigens as well as an increased immune infiltration; the reverse is true for tumors resistant to immunotherapy. In the future, Subramanian aims to determine how the immune system recognizes neoantigens and how to distinguish between activated and exhausted immune cells. “Our findings could advance the development of new immunotherapies and support clinicians in making more informed treatment decisions for their patients,” Subramanian said. “The importance of leveraging a patient’s own immune system against cancer lies in the fact that immune-based therapies can provide effective treatments with limited toxicity.”
Subramanian and his team have only begun to scratch the surface of the immune systems’ potential. “Our understanding of cancer remains somewhat primitive, our inherent immune system may be the answer hiding in plain sight,” Subramanian said. “We will pursue new therapies, improve patient outcomes and save more lives.”