Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer

Zachary D Wallen ¹, Heidi Ko ¹, Mary K Nesline ¹

⁰Labcorp Oncology, Medical Oncology, Durham, NC, United States.

Frontiers in Immunology +

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July 8, 2024

View abstract on PubMed

Summary

Younger non-small cell lung cancer patients have unique genomic and immune profiles. Age and sex significantly impact immunotherapy effectiveness, highlighting the need for personalized treatment strategies.

Area Of Science

Oncology
Genomics
Immunology

Background

Younger patients (<50 years) with non-small cell lung cancer (NSCLC) exhibit distinct clinicopathological and genomic features.
Limited research exists on age-related differences in the tumor immune microenvironment and the impact of sex in younger NSCLC patients.

Purpose Of The Study

To compare genomic alterations and immunogenic markers between younger and older NSCLC patients, considering sex differences.
To evaluate the combined effect of age and sex on survival outcomes in NSCLC patients receiving immunotherapy with or without chemotherapy.

Main Methods

Retrospective analysis of 8,230 NSCLC patients, categorizing them as younger (<65 years) or older (≥65 years).
Analysis of genomic alterations and immune markers, with a focus on sex-based comparisons.
Validation in an independent cohort to assess age and sex interactions with treatment outcomes.

Main Results

Younger NSCLC patients displayed distinct genomic profiles and reduced immune activation, particularly males.
Younger males on immunotherapy alone had worse survival than older males; chemotherapy mitigated this.
Younger females on immunotherapy plus chemotherapy showed improved survival compared to older females.

Conclusions

Comprehensive genomic and immune profiling (CGIP) is valuable for tailoring NSCLC treatment in younger patients.
Findings support broader CGIP coverage for younger patients with advanced NSCLC to personalize therapy.

Keywords:

NSCLC cancer gene expression genomics immune profiling inflammation non-small cell lung cancer tumor microenvironment