Mark Awad: Our group’s effort to elucidate mechanisms of resistance to PD-1 immunotherapy in lung cancer

Mark Awad, Director of Clinical Research, Associate Professor of Thoracic Oncology at the Dana-Farber Cancer Institute, shared on X:

“Now out in Journal of Clinical Oncology, led by the outstanding Biagio Ricciut and Giuseppe Lamberti, is our group’s effort to elucidate mechanisms of resistance to PD-1 immunotherapy in lung cancer.

We examined pre- and post-immunotherapy biopsies in comparison to patients who only received intervening chemotherapy and/or targeted therapy. Among patients with resistance to immunotherapy, we found:

1) Acquired mutations in STK11, KEAP1, and beta-2 microglobulin (B2M), among other genomic alterations, after resistance to immunotherapy.

2) Acquired loss of HLA class I expression in several cases.

3) Distinct changes in the immunophenotype, marked by decreases in intratumoral lymphocytes, decreased engagement between PD-L1 and PD-1, and increased distance between tumor cells and T cells.

Check out the paper for additional details on the heterogeneity of potential resistance mechanisms. A huge thank you to all our collaborators across Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Harvard T.H. Chan School of Public Health, João Alessi, Liam F. Spurr, Federica Pecci, Alessandro Di Federico, Deepti Venkatraman, Adriana Barrichello, Lynette Sholl, Renato Umeton, Malini Gandhi and many others.”

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Source: Mark Awad/X