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Abstract Background: Discoidin domain receptor 1 (DDR1) is highly expressed in epithelial cancers and has been implicated in tumor growth, invasion, and lack of response to therapy. DDR1 contributes to immune exclusion by promoting tumor collagen alignment in in vivo models. However, it is unclear how DDR1 expression impacts immune cell infiltration in human tumors. A first-in-human trial of PRTH-101, a DDR1-targeted therapeutic antibody, is underway. Establishing a correlation between DDR1 expression and immune infiltration in the tumor microenvironment (TME) will shed light on the role of DDR1 in the TME and inform indication and patient selection strategies for DDR1-targeted therapies. Methods: Adjacent formalin fixed paraffin embedded slides from colorectal (CRC), non-small cell lung (NSCLC), ovarian (OC), pancreatic (PDAC), and triple-negative breast cancers (TNBC) were stained by H0. 001-0. 01) at a pan-cancer level. While the degree of the correlation varied between tumor indications by IES immune cell type, pancreatic cancer exhibited the strongest correlation between the lymphocyte-based IES and DDR1 mRNA and protein expression (R: 0. 48-0. 54, adjusted p: 0. 04-0. 07). DDR1 mRNA was also moderately correlated with lymphocyte IES in NSCLC and TNBC (R: 0. 37-0. 48, adjusted p: 0. 12-0. 14). Conclusions: We developed a continuous scoring method to quantify the degree of immune exclusion in tumors based on the spatial distributions of lymphocytes, CD8+ T cells, and CD45+ immune cells from H Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2916.
Sher et al. (Fri,) studied this question.