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Pretreatment emotional distress and peripheral biomarkers predict immune checkpoint inhibitor response in people with advanced inoperable gastroesophageal cancer
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  • Published: 26 January 2026

Pretreatment emotional distress and peripheral biomarkers predict immune checkpoint inhibitor response in people with advanced inoperable gastroesophageal cancer

  • Runze Huang  ORCID: orcid.org/0000-0002-7747-48831,2,3 na1,
  • Guodong Nie4 na1,
  • Anlong Li3,5 na1,
  • Xueting Ding  ORCID: orcid.org/0009-0006-4749-33856 na1,
  • Mengqian Liu5,7 na1,
  • Ling Cheng8,
  • Senbang Yao3,
  • Han Ge5,9,
  • Jiaying Chai3,5,
  • Yingxue Jia3,5,
  • Lijun Liu3,5,
  • Zhonglian Huang3,
  • Huaidong Cheng10,11 &
  • …
  • Mingjun Zhang  ORCID: orcid.org/0000-0001-6422-12573 

Communications Medicine , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cancer immunotherapy
  • Gastrointestinal cancer
  • Tumour biomarkers

Abstract

Background

Emotional distress (ED) has been demonstrated to compromise immune responses against tumors; however, few clinical studies have explored its influence on the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients, especially those with gastroesophageal cancer (GEC). Additionally, reliable biomarkers for predicting the response to immunotherapy remain elusive. This study was aimed at investigating whether ED affects the outcomes of immunotherapy in advanced GEC patients and identifying potential biomarkers predictive of immunotherapy efficacy.

Methods

This prospective observational cohort study enrolled 84 patients with advanced, treatment-naïve, and inoperable GEC. ED was evaluated at baseline using the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-item Scale. The primary endpoint was Progression-Free Survival (PFS), while the secondary endpoint was Disease Control Rate (DCR).

Results

Patients with baseline ED exhibit significantly shorter median PFS (7.8 months vs. 14.0 months, HR = 2.59, 95% CI: 1.35-4.97, P = 0.004) and a lower DCR (39.5% vs. 68.3%, OR = 3.21, 95% CI: 1.29–7.98, P = 0.012) compared to those without ED. Exploratory analyses further demonstrate that both pre- and post-treatment peripheral inflammatory markers (PIMs) are independently and jointly associated with survival outcomes in combination with ED.

Conclusions

This prospective study demonstrates that ED and elevated PIMs significantly impair ICI efficacy in advanced GEC. The synergistic interaction between ED and PIMs suggests underlying psycho-inflammatory mechanisms affecting treatment outcomes. These findings establish the clinical importance of integrating routine psychological assessment and PIMs monitoring in cancer patients receiving immunotherapy.

Plain language summary

This study explored how stress and inflammation affect treatment outcomes in patients with advanced stomach or esophageal cancer receiving a type of treatment called immunotherapy. We aimed to understand why some patients respond better to these drugs and whether emotional health plays a role. We followed 84 patients, using questionnaires and blood tests to measure stress and inflammation before treatment. Patients with high stress before treatment saw faster cancer progression (7.8 vs. 14 months) and poorer responses to immunotherapy. High inflammation levels further worsened outcomes, especially when combined with stress. These results highlight that reducing stress and monitoring inflammation before treatment could help doctors tailor immunotherapy plans, potentially improving survival and quality of life for cancer patients.

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Data availability

The source data underlying the figures are provided as Supplementary Data 2 alongside this manuscript. Specifically, the source data for Fig. 3 are available in “PFS by pretreatment ED”, for Fig. 4 in “PFS subgroup analysis” and for Fig. 5 in “PFS by each significant biomark”. Additional supporting data not included in Supplementary Data 2, as well as the complete datasets generated and/or analysed during this study, are not publicly available due to patient confidentiality requirements and institutional data protection policies. Deidentified individual patient-level clinical data are available under restricted access upon reasonable request. All requests for datasets should be directed to the corresponding author, CH (chd1975ay@126.com) and will be responded to within 2 weeks. Requests will be reviewed to determine whether the request is subject to any intellectual property or confidentiality obligations. Patient-related data requires the requesting researcher to sign a data access agreement, and data will be shared in aggregate form if there is no reasonable likelihood of participant reidentification.

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Acknowledgements

We would like to thank all the patients who participated in the study. This work was supported by the National Natural Science Foundation of China (grant no. 82573690 to H.D. Cheng), the Health Research Project of Anhui Province (grant no. AHWJ2023A20149 to L. Cheng), and the 2024 Take-Off Project of Shenzhen Hospital of Southern Medical University (grant no. 23H3ATF01 to H.D. Cheng).

Author information

Author notes

  1. These authors contributed equally: Runze Huang, Guodong Nie, Anlong Li, Xueting Ding, Mengqian Liu.

Authors and Affiliations

  1. School of Medicine, Tongji University, Shanghai, China

    Runze Huang

  2. Department of Medical Oncology, Shanghai Pulmonary Hospital, Shanghai, China

    Runze Huang

  3. Department of Oncology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

    Runze Huang, Anlong Li, Senbang Yao, Jiaying Chai, Yingxue Jia, Lijun Liu, Zhonglian Huang & Mingjun Zhang

  4. Gamma Knife Unit, Tumor Center, Huainan Chaoyang Hospital, Huainan, Anhui, China

    Guodong Nie

  5. Anhui Medical University, Hefei, Anhui, China

    Anlong Li, Mengqian Liu, Han Ge, Jiaying Chai, Yingxue Jia & Lijun Liu

  6. Department of Health, Society, & Behavior, Joe C. Wen School of Population & Public Health, Susan and Henry Samueli College of Health Sciences, University of California, Irvine, Irvine, CA, USA

    Xueting Ding

  7. Department of Nephrology, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

    Mengqian Liu

  8. Department of Oncology, Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China

    Ling Cheng

  9. School of Nursing, Anhui Medical University, Hefei, Anhui, China

    Han Ge

  10. The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China

    Huaidong Cheng

  11. Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China

    Huaidong Cheng

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Contributions

H.R., N.G. and L.A. planned the study. N.G., L.A., G.H., C.J., J.Y., L.L. and H.Z. took part in the process of data collection. H.R. carried out analysis, interpreted results and drafted the manuscript. D.X., L.M., C.L., Y.S., H.Z., C.H. and Z.M. revised it for critically important intellectual content. All authors gave final approval of the version to be published.

Corresponding authors

Correspondence to Zhonglian Huang, Huaidong Cheng or Mingjun Zhang.

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Huang, R., Nie, G., Li, A. et al. Pretreatment emotional distress and peripheral biomarkers predict immune checkpoint inhibitor response in people with advanced inoperable gastroesophageal cancer. Commun Med (2026). https://doi.org/10.1038/s43856-025-01358-9

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  • Received: 16 May 2025

  • Accepted: 22 December 2025

  • Published: 26 January 2026

  • DOI: https://doi.org/10.1038/s43856-025-01358-9

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