Immunotherapy Resistance Remains a Puzzle

Jennifer L.W. Fink
Published: Friday, Dec 15, 2017
Dr. Antoni Ribas

Antoni Ribas, MD, PhD
Checkpoint blockade immunotherapy has been hailed as a significant advance in anticancer treatment. Yet only a subset of patients experience long-term cancer remission as a result of these therapies, because a significant number of those who initially respond eventually develop resistance.

Politi’s team is studying tumor specimens before treatment is administered and after resistance develops to determine differences at the DNA or RNA level, and in proteins and immune cells. They are using patient-derived tumor xenografts to understand the impact of the alterations they identify. “We want to be able to validate them functionally,” she said.

Definition and Magnitude of Resistance

Antoni Ribas, MD, PhD, a leading authority on immunotherapy and a Giants of Cancer Care® awardwinner, and colleagues have defined 3 types of resistance to immunotherapy that have been manifested in clinical scenarios: (1) primary resistance, in which the cancer fails to respond to therapy; (2) adaptive immune resistance, in which cancer cells are recognized by the immune system but develop ways to protect themselves from attack (may be primary resistance, mixed response, or acquired resistance); and (3) acquired resistance, in which a cancer responds to immunotherapy but progresses after a period of time.1


Table. Checkpoint Immunotherapy Response Rates and Duration in Pivotal Trials2

Checkpoint Immunotherapy Response Rates
Long-term survival rates for patients with melanoma or non–small cell lung cancer (NSCLC) who were treated with anti–PD-1 inhibitors in early clinical trials exceed what would have been expected with standard therapies in these disease settings. Forty percent of patients with advanced melanoma who started taking pembrolizumab during the clinical trial that led to its initial approval were alive after 3 years, researchers reported at the 2016 American Association of Clinical Oncology Annual Meeting.3
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