2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.02 Watson

PP01.02 Watson - Poster

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The document discusses the impact of high copy number gain (CNG) of HER2, KRAS, and MET on the tumor immune microenvironment (TME) and response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). The study found that HER2 CNG-high status is associated with decreased tumor mutational burden (TMB), PD-L1 positivity, and a T-cell inflamed transcriptomic signature compared to MET or KRAS CNG-high tumors. Additionally, HER2 CNG-high status is linked to lower survival post-ICI compared to CNG-low tumors, unlike KRAS or MET amplifications. The research also highlights differences in immune cell fractions between CNG-high tumors, with the HER2-H driver subgroup showing lower prevalence of T cell-inflamed tumors. The findings suggest that CNG-high tumors could impact TME markers and survival after ICI treatment, emphasizing the need for further exploration into the therapeutic uncertainties surrounding CNG-high tumors and their response to different therapies. Future directions include prospective studies on the impact of CNG on ICI response, consideration of co-mutations and clinical correlations, and exploration of alternative therapies for HER2-H/driver-negative tumors.

Keywords

high copy number gain

HER2

KRAS

MET

tumor immune microenvironment

immune checkpoint inhibitors

non-small cell lung cancer

tumor mutational burden

PD-L1

T-cell inflamed signature