Unraveling impact and potential mechanisms of baseline pain on efficacy of immunotherapy in lung cancer patients: a retrospective and bioinformatic analysis

Front Immunol. 2024 Nov 25:15:1456150. doi: 10.3389/fimmu.2024.1456150. eCollection 2024.

Abstract

Objective: Pain is a prevalent discomfort symptom associated with cancer, yet the correlations and potential mechanisms between pain and the efficacy of cancer immunotherapy remain uncertain.

Methods: Non-small cell lung cancer (NSCLC) patients who received immune checkpoint inhibitors (ICIs) in the inpatient department of Guangdong Provincial Hospital of Chinese Medicine from January 1, 2018, to December 31, 2021, were retrospectively enrolled. Through cox regression analysis, prognostic factors and independent prognostic factors affecting the efficacy of ICIs were identified, and a nomogram model was constructed. Hub cancer-related pain genes (CRPGs) were identified through bioinformatic analysis. Finally, the expression levels of hub CRPGs were detected using an enzyme-linked immunosorbent assay (ELISA).

Results: Before PSM, a total of 222 patients were enrolled in this study. Univariate and multivariate cox analysis indicated that bone metastasis and NRS scores were independent prognostic factors for the efficacy of ICIs. After PSM, a total of 94 people were enrolled in this study. Univariate cox analysis and multivariate cox analysis indicated that age, platelets, Dnlr, liver metastasis, bone metastasis, and NRS scores were independent prognostic factors for the efficacy of ICIs. A nomogram was constructed based on 6 independent prognostic factors with AUC values of 0.80 for 1-year, 0.73 for 2-year, and 0.80 for 3-year survival. ELISA assay results indicated that the level of CXCL12 significantly decreased compared to baseline after pain was relieved.

Conclusion: Baseline pain is an independent prognostic factor affecting the efficacy of ICIs in lung cancer, potentially through CXCL12-mediated inflammation promotion and immunosuppression.

Keywords: C-X-C motif chemokine ligand 12; baseline pain; immunotherapy; lung cancer; peripheral inflammatory cells; prognostic model.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Computational Biology* / methods
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / therapy
  • Male
  • Middle Aged
  • Nomograms
  • Prognosis
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Immune Checkpoint Inhibitors

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Key Research and Development Program of China (2023YFC3503303), the National Natural Science Foundation of China (NSFC, grant number 82004447), the Major Innovation Technology Construction Project of Synergistic Chinese Medicine and Western Medicine of Guangzhou (grant number 2023-2318), Guangzhou Municipal Science and Technology Bureau, China (grant number 2024A03J0730 and 2023A04J0452) and The Project of Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome (grant number YN2023ZH03).