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 Rezapour; Daniel Rydbeck; Fabian Byvald; Viktor Tasselius; Gustaf Danielsson; Eva Angenete; Ulf Yrlid

doi:10.1080/2162402X.2023.2209473

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

Oncoimmunology. 2023 May 10;12(1):2209473. doi: 10.1080/2162402X.2023.2209473. eCollection 2023.

Authors

Azar Rezapour¹, Daniel Rydbeck^{2

3}, Fabian Byvald¹, Viktor Tasselius^{3

4}, Gustaf Danielsson⁵, Eva Angenete^{2

3}, Ulf Yrlid¹

Affiliations

¹ Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
² Department of Surgery, Region Västra Götaland, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden.
³ Department of Surgery, SSORG - Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Department of Clinical Pathology and Genetics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

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.

Keywords: Granzyme B; Immunoscore; MxA; Neoadjuvant treatment; Rectal Cancer; Tumor infiltrating lymphocytes; Type I Interferon; γδ T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma* / drug therapy
Biomarkers / metabolism
Biopsy
CD8-Positive T-Lymphocytes / metabolism
Humans
Interferon Type I* / metabolism
Neoadjuvant Therapy / methods
Rectal Neoplasms* / diagnosis
Rectal Neoplasms* / therapy

Substances

Interferon Type I
Biomarkers

Grants and funding

This work was funded by Mary von Sydow’s Research Fund, Lion’s Cancer Research Fund of Western Sweden, Swedish Cancer Society, 2018/724, 21 1570 Pj, 19 0333 Pj, and 22 2265 Pj Swedish State under the agreement between Swedish government and the county councils—the ALF agreement, ALFGBG-723231, and ALFGBG-716581; Swedish Research Council, 2017-01103 and 2021-01025.