A type I interferon footprint in pre-operative biopsies is an independent biomarker that in combination with CD8+ T cell quantification can improve the prediction of response to neoadjuvant treatment of rectal adenocarcinoma

• Published in: Oncoimmunology Vol. 12; no. 1; p. 2209473
• Main Authors: Rezapour, Azar, Rydbeck, Daniel, Byvald, Fabian, Tasselius, Viktor, Danielsson, Gustaf, Angenete, Eva, Yrlid, Ulf
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2023; Taylor & Francis Group
• Subjects: Adenocarcinoma - drug therapy; Biomarkers - metabolism; Biopsy; cancer; CD8-Positive T-Lymphocytes - metabolism; gamma delta T cells; Granzyme B; Humans; immunity; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Immunoscore; Interferon Type I - metabolism; MxA; Neoadjuvant Therapy - methods; Neoadjuvant treatment; Oncology; Original Research; Rectal Cancer; Rectal Neoplasms - diagnosis; Rectal Neoplasms - therapy; Tumor infiltrating lymphocytes; Type I Interferon; γδ T cells; γδ T cells; Granzyme B; Tumor infiltrating lymphocytes; Immunoscore; MxA; Type I Interferon; Rectal Cancer; Neoadjuvant treatment
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2023.2209473

Tailored treatment for patients with rectal cancer requires clinically available markers to predict their response to neoadjuvant treatment. The quantity of tumor-infiltrating lymphocytes (TILs) in pre-operative tumor biopsies has been suggested to predict a favorable response, but opposing results exist. A biopsy-adapted Immunoscore (IS B ) based on TILs has recently emerged as a promising predictor of tumor regression and prognosis in (colo)rectal cancer. We aimed to refine the IS B for prediction of response using multiplex immunofluorescence (mIF) on pre-operative rectal cancer biopsies. We combined the distribution and density of conventional T cell subsets and γδT cells with a type I Interferon (IFN)-driven response assessed using Myxovirus resistance protein A (MxA) expression. We found that pathological complete response (pCR) following neoadjuvant treatment was associated with type I IFN. Stratification of patients according to the density of CD8 + in the entire tumor tissue and MxA + cells in tumor stroma, where equal weight was assigned to both parameters, resulted in improved predictive quality compared to the IS B . This novel stratification approach using these two independent parameters in pre-operative biopsies could potentially aid in identifying patients with a good chance of achieving a pCR following neoadjuvant treatment.