K. Cheruvu1, R. Smith1,2, A.G. Pachimatla1, J. Barbi1,2, S. Yendamuri1 1Roswell Park Cancer Institute, Department Of Thoracic Surgery, Buffalo, NY, USA 2Roswell Park Cancer Institute, Department Of Immunology, Buffalo, NY, USA
Introduction:
Regulatory T cells (Tregs) create an immunosuppressive environment that facilitates tumor progression. PD-1 positivity of Tregs is known to be indicative of increased activation status and contributes to poor disease and therapy outcomes in lung cancer. However, it is unclear if Treg activation in the post-resection airways of patients with lung cancer is associated with recurrence. We therefore measured PD-1 expression by bronchoalveolar lavage (BAL)-Treg to examine the association with recurrence-free survival (RFS) in lung cancer patients.
Methods:
We conducted a retrospective review of 50 patients with stage 1, 2, or 3 Lung Cancer who underwent resection surgery (lobectomy) between 2021-2023. Data on demographics, histology and stage were collected . BAL samples obtained at the time of surgical resection from the noncancer side were immunophenotyped using a high dimensional spectral flow cytometry (Cytek) platform. Demographic and clinical characteristics of patients with a high and low proportion of BAL-Tregs expressing PD-1 (above, below median) in their BALs were compared using paired-samples t test and Fischer’s exact test for continuous and categorical variables, respectively. Association between PD-1+ BAL-Treg frequencies and recurrence-free survival (RFS) was analyzed using Kaplan Meier and Cox proportional hazards models using age, sex, tumor stage, histology, smoking history, BMI, and Treg PD-1 level as covariates.
Results:
Patients were categorized based on high (≥4.47%, n= 25) and low (<4.47%, n= 25) frequencies of PD-1+ BAL-Tregs. In the study cohort (n=50; recurrence = 13, non-recurrence = 37), the recurrence group had significantly more PD-1 High patients than the non-recurrent group (62% vs. 46%, p=0.05). Univariable analysis trended towards significance and multivariable analyses revealed statistically significant negative association between PD-1+ BAL-Tregs and RFS (Hazard Ratio [HR] = 2.78; 95% Confidence Interval [CI] = 0.90-8.58, p=0.053 and HR = 7.26, 95% CI = 1.02-51.47, p = 0.047, respectively) [Figure 1]. Low BMI and early stage also significantly improved RFS (HR = 0.89, p = 0.021; HR = 0.063, p = 0.007).
Conclusion:
We demonstrate that higher proportions of PD-1+ Tregs are associated with a reduced RFS after lobectomy in non-metastatic lung cancer. These findings suggest that the immune status of the non-tumor bearing lung is important for predicting tumor recurrence. They also suggest these Tregs may serve as a potential therapeutic target for development of novel adjuvant therapy strategies in lung cancer.