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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Treatment Resistant Cancers02:56

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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Related Experiment Video

Updated: Jan 13, 2026

Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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Neoadjuvant Immunochemotherapy in Resectable NSCLC With SMARCA4 Alterations.

Li-Shan Peng1, Qian Cui2, Chao Zhang1

  • 1Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer, Guangzhou, China.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|October 29, 2025
PubMed
Summary

Neoadjuvant immunochemotherapy shows promise in SMARCA4-altered non-small cell lung cancer (NSCLC), particularly in squamous cell carcinoma. However, other subtypes, especially those with KRAS mutations, present a distinct immune-cold, high-risk profile.

Keywords:
ImmunotherapyNeoadjuvantNon–small cell lung cancerSMARCA4

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Area of Science:

  • Oncology
  • Genomics
  • Immunotherapy

Background:

  • Neoadjuvant immunochemotherapy improves outcomes in non-small cell lung cancer (NSCLC).
  • The efficacy of this treatment in SMARCA4-altered NSCLC, a poor-prognosis subset, is not well understood.
  • SMARCA4 alterations are associated with aggressive disease and poorer survival in lung adenocarcinoma.

Purpose of the Study:

  • To evaluate the efficacy of neoadjuvant immunochemotherapy in patients with SMARCA4-altered NSCLC.
  • To investigate the clinical characteristics and tumor immune microenvironment of SMARCA4-altered NSCLC.
  • To identify factors associated with treatment response and survival in this patient population.

Main Methods:

  • Retrospective analysis of 29 patients with SMARCA4-altered NSCLC treated with neoadjuvant immunochemotherapy.
  • Next-generation sequencing for comprehensive genomic profiling.
  • Analysis of tumor immune microenvironment using molecular functional portraits.
  • Comparison with The Cancer Genome Atlas (TCGA) data for lung adenocarcinoma.

Main Results:

  • Objective response rate of 70.4% and pathologic complete response (pCR) rate of 51.7% in the overall cohort.
  • Significantly higher pCR rates in squamous cell carcinoma (83.3%) compared to adenocarcinoma (28.6%).
  • SMARCA4-altered lung adenocarcinoma showed worse survival and immune-cold characteristics, with KRAS/KEAP1/STK11 co-mutations predicting early relapse.

Conclusions:

  • SMARCA4-altered NSCLC is a heterogeneous disease with varying responses to immunochemotherapy.
  • Squamous cell carcinoma demonstrates high sensitivity to neoadjuvant immunochemotherapy.
  • Non-squamous subtypes, particularly those with KRAS and KEAP1/STK11 co-mutations, represent an immune-cold, high-risk subgroup requiring distinct therapeutic strategies.