Interaction between cancer associated fibroblasts and cancer cells influence immune infiltrate and is modulated by therapeutic agents

Abstract

Background: Cancer associated fibroblasts (CAFs) can help tumours evade immune-surveillance by affecting the immune cell infiltrate, mainly via secretion of cytokines and chemokines. CAFs phenotype and spatial relationship to cancer cells alter the kind of cytokines and chemokines they secrete. In Squamous cell carcinoma (SCC), cancer-associated fibroblasts can trigger a Type I Interferon when in direct cell-cell contact with cancer cells.Methods: Bioinformatics: we used publicly available RNAseq data from The Cancer Genome Atlas (TCGA) for Head and Neck Squamous Cell Carcinoma (HNSCC 518 tumours. [http://firebrowse.org/]) . Using the RSEM normalized gene expression, we divided tumours according to the expression of CAF markers not expressed in cancer cells (FAP, Thy-1, s100a4and PDGFRb). We used CIBERSORT to estimate the abundance of immune cells in the tumours. In vitro assays: we used A431 (human SCC cell line) and CAFs extracted from a human tumour in our lab. We cultured them in either direct cell-to-cell contact or using a transwell. We treated the A431 with AZD6738 (ATR inhibitor), 5-aza-2′-deoxycytidine and cisplatin. We analysed mRNA expression of different interferon response genes by qRT-PCR.