Study of tumor immune contexture in patients with squamous carcinomas of head and neck in the Indian population – A pilot study

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC)in India is strongly associated with use of tobacco and areca nut products. Most patients present in their fifth and sixth decades at advanced stages, compared with age at onset in the North American population. These differences in etiology and onset suggest potential differences in pathogenesis and immuno-biology. During immune evasion by tumor, receptors such as CTLA-4, LAG-3, TIM-3, and programmed cell death protein 1 (PD-1), have been identified on exhausted and dysfunctional lymphocytes and shown to be upregulated in tumor cell lines and tissues by transcriptional methods. However, there is limited information currently available in the Indian population in this regard. In our study we intended to define the immune contexture in HNSCC cases by characterizing the tumor infiltrating lymphocytes (TILs) and the intra-tumoral heterogeneity of other relevant markers by immunohistochemistry (IHC) methods. Determining the prognostic and predictive value of these markers may guide the development of drugs for this cancer type, as it has for other carcinomas. It could help clinicians better predict clinical outcomes and thereby make more informed therapeutic decisions. Method(s): 50 cases of HNSCC were studied for expression of immune cell markers such as PDL1, IDO, CD8, FOXP3, LAG-3by IHC methods onformalin fixed paraffin embedded (FFPE) sections. The whole slide images of the stained slides were analyzed manually and by digital algorithms. Frequency and intensity of PDL1 and IDO were evaluated in both immune cells (IC) and tumor cells (TC). Proximity analyses between PDL1+ IC/IDO+IC with FOXP3+IC/CD8+ IC/CD3+ IC were performed using standard morphometric approaches and the pattern of immune cell infiltration documented. Result(s): Preliminary analysis reveals high concordance between pathologists for all markers and between manual and digital scoring methods. Significant positive correla-tion between FOXP3+IC and PDL1+ IC and IDO+ TC with FOXP3IC is seen with overall percentage of PDL1 and FOXP3 positive immune cells being low as compared to IDO and CD8. Conclusion(s): As these changes, at least in part, mirror the immune contexture of HNSCC studied in the North American population, it is surmised that treatment approaches based on PD1 blockade are likely to also provide significant benefit to Indian patients. More detailed analysis is being done. Data will be correlated with pathological stage, tumor and serum kynurenine levels, and two year follow up information, wherever available. Some of this work is being presented here.