Abstract Introduction: Immune checkpoint inhibitors has improved outcome of recurrent /metastatic head and cancer (rmHNSCC) . Benefit is seen in around 20% pf patients and is proportionate to PD-L1 expression. We evaluated correlation between PD-L1, Desmocollin-3 (DSC3) and stromal tumor infiltrating lymphocytes (TIL) to explore possibility of using DSC3 specific therapy along rmHNSCC . DSC3 is a predictive biomarker for an investigational product CADI-05. Methods: Samples from patients with rmHNSCC were evaluated PD-L1 expression using standard protocol and expressed as combined proportion score (CPS) and tumor proportion score ( TPS) . DSC3 expression was evaluated as tumor proportion score (TPS) by immunohistochemistry, using mouse anti-DSC3 monoclonal antibody (Progen, Heidelberg, Germany Cat#61093 dilution: 1:50) following removal of paffinization of formalin-fixed, paraffin-embedded tissue. TIL was evaluated after staining with hematoxylin and eosin and expressed as a percentage of total cells. All evaluated samples were received after informed consent of patients. Results: Total of seventy (70) samples were evaluated between September 2023 to May 2025 for PD-L1, DSC3 and TIL. PD-L1 expression as CPS and TPS was observed in 77% and 51% of samples. PD-L1 values ranged from 0-95% ( CPS) and 0-95%(TPS). DSC3 expression was observed in 93% of samples. DSC3 (TPS) values ranged from 0-80%. No correlation was found between PD-L1(CPS) and DSC3 expression (Spearman correlation coefficient r = -0.1432, p = 0.3846; 95% Confidence interval = -0.4389 to 0.1805). There was a moderate negative correlation (r= -0.3) between PD-L1(TPS) and DSC3. All PD-L1 negative samples expressed DSC3.Mean and median DSC3 expression values were not different between PD-L1 positive and negative samples. Based on expression level TIL were grouped as samples having TIL ≥ 10% and 10%. TIL ≥ 10% were observed in 40% of evaluated samples. All samples expressing PD-L1(CPS and TPS) as well as DSC3 had TIL ≥ 10% . TIL were absent in five samples and all expressed DSC3 from 10-40%. Conclusion: DSC3 is expressed in 93% of rmHNSCC , irrespective of PD-L1 and TIL expression suggesting DSC3 specific therapy may be useful in management of patients with rmHNSCC with absent/low PD-L1 and or TIL . Citation Format: Vedanti Newaskar, Shivani Sharma, Bakulesh M. Khamar. Correlation between PD-L1, desmocollin 3, and stromal lymphocytes in recurrent head and neck squamous cell carcinomas abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7721.
Newaskar et al. (Fri,) studied this question.