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April 23, 2026Clinical and Translational Medicine0 citationsOpen Access

The landscape of responses to neoadjuvant immunotherapy in resectable Kirsten rat sarcoma viral oncogene homolog‐mutant lung adenocarcinoma: Clinical heterogeneity and correlative immunologic analysis

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SWS WuJNJiheng NiuXCXiaowei Chen

Key Points

  • This research aims to explore how KRAS mutations affect immune responses to neoadjuvant immunotherapy in lung adenocarcinoma.
  • Comparative analysis of pathological responses and survival rates between KRAS-mutant and wildtype patients.
  • Immunologic profiling to identify CD4T_Treg_TNFRSF4 subsets in non-responders and Th1/Bex networks in responders.
  • KRAS-mutant patients show poorer responses and survival rates after immunotherapy compared to KRAS-wildtype patients.
  • A specific CD4T_Treg_TNFRSF4 subset is associated with an immunosuppressive environment in non-responders.
  • Successful responders exhibit a balance between Th1 cells and a novel exhausted-like B-cell state.

Abstract

KRAS-mutant LUAD patients exhibit inferior pathological responses and survival after neoadjuvant immunotherapy compared to KRAS-wildtype patients. A CD4TTregTNFRSF4 subset is enriched in non-responders, defining an immunosuppressive microenvironment. Responders are characterized by a synergistic network between Th1 cells and a novel exhausted-like B-cell (Bex) state. The balance between immunosuppressive Tregs and the Th1/Bex axis determines therapeutic efficacy in KRAS-mutant LUAD.

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Cite This Study

Wu et al. (2026) studied this question.

synapsesocial.com/papers/69e9b80e85696592c86eb911https://doi.org/10.1002/ctm2.70670
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