Evidence map›Paper›PMID 42011021›Full record

ArticleClinical and translational medicine2026

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

Sikai Wu, Jiheng Niu, Xiaowei Chen, Jinfei Li, Quanying Tang, Zhenlin Yang, Shugeng Gao

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Sikai WuDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jiheng NiuSchool of Basic Medical Sciences, Tsinghua University, Beijing, China.
Xiaowei ChenDepartment of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Jinfei LiDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Quanying TangDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhenlin YangDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Shugeng GaoDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Funding

Beijing Natural Science Foundation 7242114CAMS Innovation Fund for Medical Sciences (CIFMS) 2021-I2M-1-015CAMS Innovation Fund for Medical Sciences (CIFMS) 2024-I2M-C&T-C-008CAMS Innovation Fund for Medical Sciences (CIFMS) 2024-I2M-ZH-005CAMS Innovation Fund for Medical Sciences (CIFMS) 2025-I2M-C&T-B-054CAMS Innovation Fund for Medical Sciences (CIFMS) 2025-I2M-QN-004CAMS Innovation Fund for Medical Sciences (CIFMS) 2025-I2M-XHXX-043Central Health Research Key Projects 2022ZD17National High Level Hospital Clinical Research Funding 2025-LYZX-C-A02National Key R&D Program of China 2021YFC2500900National Natural Science Foundation of China 82273129National Natural Science Foundation of China 82472808National Natural Science Foundation of China 82522069Young Elite Scientists Sponsorship Program by CAST 2022QNRC001Young Elite Scientists Sponsorship Program by CAST 2024QNRC001
6 · The paper itself

Abstract

backgroundKirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma (LUAD) typically demonstrates limited response to neoadjuvant immunotherapy (NIT). Elucidating the immune determinants that differentiate responders from non-responders was critical for optimizing immunotherapy strategies. This study aimed to characterize the tumour microenvironment features of KRAS-mutant LUAD following neoadjuvant programmed death protein 1 (PD-1) inhibitor therapy by integrating clinical outcomes with single-cell RNA sequencing (scRNA-seq).

methodsA total of 143 patients with resectable LUAD were consecutively enrolled in this study, including 106 cases in the KRAS-wildtype cohort and 37 cases in the KRAS-mutant cohort. We systematically compared the pathological response rates, survival outcomes and recurrence patterns between the two cohorts. We performed scRNA-seq on tumour specimens from 234 real-world patients with non-small cell lung cancer. From this cohort, 48 LUAD cases were identified and stratified by KRAS mutation status (13 KRAS-mutant and 35 KRAS-wildtype patients). Cellular compositions, transcriptional features and intercellular communication networks were analysed.

resultsClinical analysis revealed that the KRAS-mutant group exhibited significantly poorer pathological responses (p = .032) and inferior long-term survival compared to the KRAS-wildtype group. We identified an immunosuppressive tumour necrosis factor receptor superfamily member 4 (TNFRSF4)-expressing regulatory T-cell (CD4T_Treg_TNFRSF4) subset enriched in non-responders, whereas responders showed increased frequencies of T helper 1 cells (Th1 cells) and a previously unrecognized exhausted-like B-cell state (Bex). Bex cells displayed impaired metabolic activity yet retained antigen presentation potential and showed extensive cellular interactions with Th1 cells, suggesting a supportive role in Th1-mediated antitumour immunity.

conclusionKRAS-mutant patients exhibited significantly poorer pathological responses, and KRAS-mutant status may independently predict survival outcomes after NIT in LUAD patients. Additionally, our study unveiled the cellular and molecular architecture underlying differential responses to NIT in KRAS-mutant LUAD, emphasizing the opposing roles of immunosuppressive Tregs and synergistic Bex-Th1 networks. HIGHLIGHTS: KRAS-mutant LUAD patients exhibit inferior pathological responses and survival after neoadjuvant immunotherapy compared to KRAS-wildtype patients. A CD4T_Treg_TNFRSF4 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.

Indexed as

Adenocarcinoma of LungImmunotherapyLung NeoplasmsNeoadjuvant TherapyProto-Oncogene Proteins p21(ras)AgedFemaleHumansMaleMiddle AgedMutationTreatment Effect HeterogeneityTumor MicroenvironmentKRAS protein, humanProto-Oncogene Proteins p21(ras)KRAS‐mutant lung adenocarcinomaneoadjuvant immunotherapysingle‐cell RNA sequencingtumour microenvironment

Identifiers

PMID42011021
PMCPMC13096693

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.