# Cellular senescence in lung cancer immune microenvironment and senotherapeutic opportunities

## TL;DR

This paper reviews how cellular senescence affects lung cancer and the immune environment, and explores new treatment strategies to target senescent cells.

## Contribution

The paper introduces a novel 'induce, then edit or eliminate' paradigm for improving lung cancer therapies through senotherapeutics.

## Key findings

- Senescence-associated secretory phenotype (SASP) modulates the tumor immune microenvironment in lung cancer.
- Senotherapeutics like senolytics and senomorphics could enhance treatment durability by targeting senescent cells.
- Senescence-linked biomarkers may guide prognosis and therapy selection in non-small cell lung cancer.

## Abstract

Cellular senescence (CS) shapes lung cancer biology by enforcing durable growth arrest while remodeling the tumor immune microenvironment (TIME) through the senescence-associated secretory phenotype (SASP). In non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs) have improved outcomes, and senescence programs can influence antigen presentation, immune cell recruitment, and adaptive resistance. This review integrates evidence from cell and animal models, patient-derived datasets, and early clinical studies to map senescent cell states across cancer immunoediting and treatment contexts. We summarize senescence phenotypes in tumor and stromal compartments, highlight SASP-driven immune modulation, and discuss senescence-linked biomarkers that may inform prognosis and therapy selection. We also evaluate emerging senotherapeutic strategies—senolytics, prodrug approaches, and SASP-modulating senomorphics—designed to pair senescence induction with selective clearance or reprogramming. Together, these concepts frame a testable “induce, then edit or eliminate” paradigm to improve durability of lung cancer therapies.

Therapeutics; immune system; cancer