CD11c+ and IRF8+ cell densities in rectal cancer biopsies predict outcomes of neoadjuvant chemoradiotherapy

Benita C Y Tse; Sarah Bergamin; Pascal Steffen; George Hruby; Nick Pavlakis; Stephen J Clarke; Justin Evans; Alexander Engel; Andrew Kneebone; Mark P Molloy

doi:10.1080/2162402X.2023.2238506

CD11c⁺ and IRF8⁺ cell densities in rectal cancer biopsies predict outcomes of neoadjuvant chemoradiotherapy

Oncoimmunology. 2023 Jul 20;12(1):2238506. doi: 10.1080/2162402X.2023.2238506. eCollection 2023.

Authors

Benita C Y Tse¹, Sarah Bergamin², Pascal Steffen¹, George Hruby², Nick Pavlakis^{3

4}, Stephen J Clarke^{3

4}, Justin Evans⁵, Alexander Engel^{4

5}, Andrew Kneebone^{2

4}, Mark P Molloy¹

Affiliations

¹ Bowel Cancer and Biomarker Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia.
² Department of Radiation Oncology, Royal North Shore Hospital, Sydney, Australia.
³ Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia.
⁴ Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Camperdown, Australia.
⁵ Colorectal Surgical Unit, Royal North Shore Hospital, Sydney, Australia.

Abstract

Approximately 20% of locally advanced rectal cancer (LARC) patients treated preoperatively with chemoradiotherapy (CRT) achieve pathologically confirmed complete regression. However, there are no clinically implemented biomarkers measurable in biopsies that are predictive of tumor regression. Here, we conducted multiplexed immunophenotyping of rectal cancer diagnostic biopsies from 16 LARC patients treated preoperatively with CRT. We identified that patients with greater tumor regression had higher tumor infiltration of pan-T cells and IRF8⁺HLA-DR⁺ cells prior to CRT. High IRF8⁺HLA-DR⁺ cell density was further associated with prolonged disease-specific survival with 83% survival at 5 y compared to 28% in patients with low infiltration. Contrastingly, low CD11c⁺ myeloid cell infiltration prior to CRT was a putative biomarker associated with longer 3- and 5-y disease-free survival. The results demonstrate the potential use of rectal cancer diagnostic biopsies to measure IRF8⁺ HLA-DR⁺ cells as predictors of CRT-induced tumor regression and CD11c⁺ myeloid cells as predictors of LARC patient survival.

Keywords: Dendritic cell; immune cell; immunophenotype; neoadjuvant chemoradiotherapy; rectal cancer.

Publication types

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

MeSH terms

Aged
Biomarkers / analysis
Biopsy
CD11c Antigen* / immunology
Cell Count
Female
Humans
Interferon Regulatory Factors* / immunology
Male
Middle Aged
Neoadjuvant Therapy
Predictive Value of Tests
Rectal Neoplasms* / diagnosis
Rectal Neoplasms* / immunology
Rectal Neoplasms* / therapy
T-Lymphocytes* / immunology
Treatment Outcome

Substances

Biomarkers
Interferon Regulatory Factors
CD11c Antigen
interferon regulatory factor-8

Grants and funding

MPM acknowledges funding support from the à Beckett Cancer Research Trust and Bowel Cancer Research Foundation Australia. PS is recipient of Cancer Institute NSW early career fellowship (2019/ECF011)..