The immune microenvironment landscape shows treatment-specific differences in rectal cancer patients

Frontiers in Immunology, vol. 13, pp. 1011498

Abstract

Neoadjuvant therapy is the cornerstone of modern rectal cancer treatment. Insights into the biology of tumor responses are essential for the successful implementation of organ-preserving strategies, as different treatments may lead to specific tumor responses. In this study, we aim to explore treatment-specific responses of the tumor microenvironment. Patients with locally advanced adenocarcinoma of the rectum who had received neo-adjuvant chemotherapy (CT), neo-adjuvant radiochemotherapy (RCT), neo-adjuvant radiotherapy with a long-interval (LRT) or short-interval (SRT) or no neoadjuvant therapy (NT) as control were included. Multiplex-immunofluorescence was performed to determine the presence of cytotoxic T-cells (T-cyt; CD3+CD8+), regulatory T-cells (T-reg; CD3+FOXP3+), T-helper cells (T-helper; CD3+CD8-FOXP3-), B cells (CD20+), dendritic cells (CD11c+) and tumor cells (panCK+). A total of 80 rectal cancer patients were included. Treatment groups were matched for gender, tumor location, response to therapy, and TNM stage. The pattern of response (shrinkage vs. fragmentation) was, however, different between treatment groups. Our analyses reveal that RCT-treated patients exhibited lower stromal T-helper, T-reg, and T-cyt cells compared to other treatment regimens. In conclusion, we demonstrated treatment-specific differences in the immune microenvironment landscape of rectal cancer patients. Understanding the underlying mechanisms of this landscape after a specific therapy will benefit future treatment decisions.

Authors 8

1. Cristina Graham Martínez corresponding

   Radboud University Medical Center

   Affiliation as printed

   Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands

2. Yari Barella

   Radboud University Medical Center

   Affiliation as printed

   Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands

3. Sonay Kuş Öztürk

   Radboud University Medical Center

   Affiliation as printed

   Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands

4. Marleen Ansems

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Radiotherapy & OncoImmunology Laboratory, Department of Radiation Oncology, Radboud University Medical Centre, Nijmegen, Netherlands

5. Mark A.J. Gorris

   Radboud University Nijmegen · Radboud University Medical Center · Oncode Institute

   Affiliation as printed

   Department of Tumor Immunology, Radboud University Medical Centre, Nijmegen, Netherlands

   Oncode Institute, Utrecht, Netherlands

6. Shannon van Vliet

   Radboud University Medical Center

   Affiliation as printed

   Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands

7. Corrie A.M. Marijnen Aachen Department of Medical Oncology

   Leiden University · Leiden University Medical Center · The Netherlands Cancer Institute

   Affiliation as printed

   Department of Medical Oncology, Leiden University Medical Centre, Leiden, Netherlands

   Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam, Netherlands

8. Irıs D. Nagtegaal

   Radboud University Medical Center

   Affiliation as printed

   Department of Pathology, Radboud University Medical Centre, Nijmegen, Netherlands