2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.05. Genomic And Immunophenotypic Landscape Of Acquired Resistance (AR) To PD-(L)1 Blockade In Non-Small Cell Lung Cancer

P1.05. Genomic And Immunophenotypic Landscape Of Acquired Resistance (AR) To PD-(L)1 Blockade In Non-Small Cell Lung Cancer

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The study analyzed the genomic and immunephenotypic landscape of acquired resistance to PD-(L)1 blockade in patients with non-small cell lung cancer (NSCLC). The researchers conducted a comprehensive analysis on paired pre- and post-treatment tumor samples from NSCLC patients who developed acquired resistance to PD-(L)1 blockade. They also included control cohorts of patients who received chemotherapy and targeted therapies. <br /><br />The results showed that diverse genomic mechanisms may contribute to acquired resistance to PD-(L)1 blockade in NSCLC. Mutations in genes such as B2M, STK11, KEAP1, JAK1, and CDKN2A/B were not detected in the control cohorts of patients who received chemotherapy or targeted therapies. <br /><br />Furthermore, the study found that the density of tumor-infiltrating lymphocytes, as well as the expression of CD8, PD-1, and HLA class I, decreased significantly at the time of acquired resistance to immunotherapy. <br /><br />Understanding the mechanisms of acquired resistance to immunotherapy is crucial for informing clinical decisions and designing clinical trials in the setting of PD-(L)1-resistant NSCLC. The study provides valuable insights into the genomic and immunephenotypic changes that occur when NSCLC patients develop acquired resistance to PD-(L)1 blockade.

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Biagio Ricciuti, Dana-Farber Cancer Institute, United States

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Speaker Biagio Ricciuti, Dana-Farber Cancer Institute, United States

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Keywords

genomic analysis

acquired resistance

PD-(L)1 blockade

NSCLC

chemotherapy

targeted therapies

genomic mechanisms

tumor-infiltrating lymphocytes

CD8

immunotherapy