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.
Azar RezapourDaniel RydbeckFabian ByvaldViktor TasseliusGustaf DanielssonEva HaglindUlf YrlidPublished in: Oncoimmunology (2023)
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.