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Peer-reviewedCC BYCurrent oncology (Toronto, Ont.)

The Role of Antinuclear Antibody in Predicting the Efficacy and Immune-Related Adverse Events of Immunochemotherapy in Esophageal Squamous Cell Carcinoma: A Real-World Analysis.

  1. 1Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
  2. 2Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.

Abstract

Background: Programmed cell death protein 1 (PD-1) inhibitor-based immunochemotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC), but accessible blood-based biomarkers associated with both treatment efficacy and the risk of immune-related adverse events (irAEs) remain limited. The presence of antinuclear antibody (ANA) in the pretreatment period may reflect host immune status; however, its clinical relevance in ESCC and its relationship with programmed death-ligand 1 (PD-L1) expression have not been fully characterized. Methods: We retrospectively enrolled 180 patients with ESCC who received PD-1 inhibitor-based immunochemotherapy. Baseline characteristics, tumor responses, survival outcomes, and irAEs were evaluated according to pretreatment ANA status. An additional sensitivity analysis was conducted among 103 patients with available PD-L1 results. Cox regression models with time-varying coefficients were applied when the proportional hazards assumption was not satisfied. Results: The ANA-positive rate was 36.67% (66/180). Compared to patients who were ANA-negative, those who were ANA-positive demonstrated superior objective response rates (71.21% vs. 46.49%, p = 0.002), longer median progression-free survival (PFS; 11.93 vs. 5.93 months) and longer median overall survival (OS; 25.20 vs. 14.77 months, both p < 0.01). In addition, they had a higher rate of all-grade irAEs (60.61% vs. 35.96%, p = 0.001), especially thyroid dysfunction (28.79% vs. 8.77%, p < 0.001). Multivariable time-varying Cox models linked ANA positivity to favorable PFS (hazard ratio [HR] = 0.14, 95% confidence interval [CI]: 0.04-0.46, p = 0.001) and OS (HR = 0.06, 95% CI: 0.01-0.52, p = 0.011). In the sensitivity cohort, ANA remained predictive for both survival endpoints, while PD-L1 did not. Conclusions: Pretreatment ANA positivity was associated with higher response rates, longer survival, and a higher incidence of irAEs in patients with ESCC receiving PD-1 inhibitor-based immunochemotherapy. These exploratory findings require prospective validation before ANA can be used to guide treatment decisions or assess individual irAE risk.

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BibTeX
@article{li2026role,
  title = {{The Role of Antinuclear Antibody in Predicting the Efficacy and Immune-Related Adverse Events of Immunochemotherapy in Esophageal Squamous Cell Carcinoma: A Real-World Analysis.}},
  author = {Ansu Li and Yue Tao and Kongcheng Wang and Haifei Yang and Jiayao Yan and Wu Sun and Wei Ren},
  journal = {Current oncology (Toronto, Ont.)},
  year = {2026},
  month = oct,
  doi = {10.3390/curroncol33100596},
  url = {https://europepmc.org/article/MED/42930163},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The Role of Antinuclear Antibody in Predicting the Efficacy and Immune-Related Adverse Events of Immunochemotherapy in Esophageal Squamous Cell Carcinoma: A Real-World Analysis.
AU  - Ansu Li
AU  - Yue Tao
AU  - Kongcheng Wang
AU  - Haifei Yang
AU  - Jiayao Yan
AU  - Wu Sun
AU  - Wei Ren
PY  - 2026
DA  - 2026/10/01
JO  - Current oncology (Toronto, Ont.)
DO  - 10.3390/curroncol33100596
UR  - https://europepmc.org/article/MED/42930163
AB  - Background: Programmed cell death protein 1 (PD-1) inhibitor-based immunochemotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC), but accessible blood-based biomarkers associated with both treatment efficacy and the risk of immune-related adverse events (irAEs) remain limited. The presence of antinuclear antibody (ANA) in the pretreatment period may reflect host immune status; however, its clinical relevance in ESCC and its relationship with programmed death-ligand 1 (PD-L1) expression have not been fully characterized. Methods: We retrospectively enrolled 180 patients with ESCC who received PD-1 inhibitor-based immunochemotherapy. Baseline characteristics, tumor responses, survival outcomes, and irAEs were evaluated according to pretreatment ANA status. An additional sensitivity analysis was conducted among 103 patients with available PD-L1 results. Cox regression models with time-varying coefficients were applied when the proportional hazards assumption was not satisfied. Results: The ANA-positive rate was 36.67% (66/180). Compared to patients who were ANA-negative, those who were ANA-positive demonstrated superior objective response rates (71.21% vs. 46.49%, p = 0.002), longer median progression-free survival (PFS; 11.93 vs. 5.93 months) and longer median overall survival (OS; 25.20 vs. 14.77 months, both p < 0.01). In addition, they had a higher rate of all-grade irAEs (60.61% vs. 35.96%, p = 0.001), especially thyroid dysfunction (28.79% vs. 8.77%, p < 0.001). Multivariable time-varying Cox models linked ANA positivity to favorable PFS (hazard ratio [HR] = 0.14, 95% confidence interval [CI]: 0.04-0.46, p = 0.001) and OS (HR = 0.06, 95% CI: 0.01-0.52, p = 0.011). In the sensitivity cohort, ANA remained predictive for both survival endpoints, while PD-L1 did not. Conclusions: Pretreatment ANA positivity was associated with higher response rates, longer survival, and a higher incidence of irAEs in patients with ESCC receiving PD-1 inhibitor-based immunochemotherapy. These exploratory findings require prospective validation before ANA can be used to guide treatment decisions or assess individual irAE risk.
SN  - 1198-0052
SN  - 1718-7729
ER  -