Work

137 Age-associated characteristics of the tumor microenvironment in patients with advanced basal cell carcinoma treated with anti-PD-1 therapy

Year: 2026

Type: conference-abstract

Abstract: Background Advanced basal cell carcinoma (aBCC) disproportionately affects elderly patients, a population that commonly exhibits immunosenescence. Anti-PD-1 therapy demonstrates efficacy in aBCC, but the association between age and the immune contexture of the tumor microenvironment (TME) in aBCC is not well characterized.Methods In this open-label, single-center phase 2 trial ( NCT03521830), 36 patients with aBCC received nivolumab (anti-PD-1) monotherapy (480 mg IV every 4 weeks). Among them, 22 had evaluable pre- and/or on-treatment biopsies (taken weeks 2-8 on-treatment) with sufficient tissue for ancillary studies (n = 35 specimens, 21 pre-treatment, 14 on-treatment). Immunohistochemical stains for immune cell subsets and checkpoints (CD3, CD8, FoxP3, CD163, CD56, PD-1, PD-L1, LAG-3, TIM-3) were performed on formalin-fixed paraffin-embedded biopsies to characterize the TME. Tumor HLA-ABC expression was also assessed. HALO image analysis software (v3.6.4134) quantified percent positive expression of markers in tumor and associated stroma. Associations between marker expression and age and sex were assessed using Pearson’s r and Wilcoxon rank-sum tests, respectively. Logistic regression assessed the relationship between age, sex, and clinical response per RECIST v1.1. Age was analyzed as a continuous variable.Results Unpaired analysis revealed a moderate inverse correlation between age and proportion of infiltrating CD3 + T-cells (r = -0.48, p = 0.033), PD-1+ immune cells (r = -0.60, p = 0.0061), and PD-1+ tumor cells (r = -0.46, p = 0.048) in pre-treatment samples. In paired pre- and on-treatment samples (n=11 pairs), older age correlated with a greater increase in CD163+ M2 macrophages (r = 0.70, p = 0.017) and PD-1+ immune cells on therapy (r=0.76, p=0.0067). No significant associations between age and the remaining markers were observed. In unpaired analyses of on-treatment samples, no significant correlations with age were observed, and marker expression did not differ significantly by sex. Among 22 patients with evaluable samples (median age 75 years [range 47–96], 50% female), response to nivolumab was 50% (11/22; 95% confidence interval: 31%-69%). There was no significant association of age or sex with clinical response.Conclusions Despite diminished CD3 + T cell infiltration at baseline and increased on-treatment expression of CD163, a marker generally associated with immunosuppression, with increasing age, responses to nivolumab were seen among older patients with aBCC. PD-1+ immune cells may reflect either early, effector T cells or exhausted T cells, and the import of PD-1 expression on tumor cells merits further study. Collectively, these findings support further investigation of the compensatory mechanisms supporting therapeutic efficacy despite immunosenescence; modalities, such as multiplex immunofluorescence and in situ hybridization, may be valuable in further characterizing the TME.Acknowledgements This work was supported by Bristol Myers Squibb and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.Trial Registration NCT03521830Ethics Approval The Johns Hopkins University School of Medicine Institutional Review Board approved this study: IRB00166274. Patients gave written informed consent.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.0137