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Clinical outcomes and tumor immune microenvironment in SMARCA4-Deficient NSCLC: A Real-World retrospective study

Wencheng Zhao1, Maoying Guan2, Huixian Zhang1

  • 1Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Lung Cancer (Amsterdam, Netherlands)
|May 1, 2026
PubMed
Abstract

Insights

SMARCA4-deficient non-small-cell lung cancer (NSCLC) shows aggressive behavior and poor survival. Immunotherapy offers benefits for selected patients, unlike chemotherapy alone, with immune microenvironment markers potentially predicting response.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • SMARCA4-deficient thoracic tumors are rare, aggressive lung cancers with poor prognoses.
  • This study compares clinical features, treatment outcomes, and immune microenvironments of SMARCA4-deficient NSCLC versus SMARCA4-intact NSCLC.

Purpose of the Study:

  • To investigate the clinical behavior and treatment outcomes of SMARCA4-deficient NSCLC.
  • To explore the immune microenvironment characteristics in SMARCA4-deficient NSCLC and their relation to treatment response.

Main Methods:

  • Retrospective study of 221 stage III-IV NSCLC patients (59 SMARCA4-deficient, 162 intact) from 2020-2024.
  • Propensity score matching (PSM) used to balance baseline characteristics.
  • Multiplex immunofluorescence (mIF) analyzed immune markers (CD4, CD8, FOXP3, CD11c, GZMB).

Main Results:

  • SMARCA4-deficient NSCLC had significantly shorter progression-free survival (PFS) and overall survival (OS) post-PSM.
  • Immunotherapy-based regimens improved PFS in SMARCA4-deficient patients compared to chemotherapy alone.
  • Immune microenvironment analysis showed CD4/CD11c prevalence and reduced FOXP3 in responders, while CD8/GZMB levels correlated with resistance.

Conclusions:

  • SMARCA4-deficient advanced NSCLC exhibits aggressive behavior and poor survival outcomes.
  • Immunotherapy-based regimens provide clinical benefit for selected SMARCA4-deficient NSCLC patients.
  • Immune microenvironment features may influence therapeutic response, requiring further large-scale validation.
Keywords:
ImmunotherapyPropensity score matchingSMARCA4-deficient NSCLCSurvival outcomesTumor microenvironment

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