Abstract 2549: Immune microenvironment landscape shows treatment-specific differences in rectal cancer patients
Authors: Martinez Cristina Graham , Barella Yari F. H. C. , Öztürk Sonay Kus , Gorris Mark A. , Marijnen Corrie A. , Nagtegaal Iris D. 
Published: June 2022

Abstract
Introduction: Neoadjuvant therapy is the backbone of modern rectal cancer treatment. More intensive therapy leads to higher complete responses, which means an organ-preservation approach can be used. Insights in the biology of tumor response are essential for a successful implementation of such strategies, as different treatments may lead to specific tumor responses. In this study we aim to explore treatment-specific responses of tumor microenvironment and how these are related to patient outcome.
Methods: Patients with adenocarcinoma of the rectum who had received one of five different treatment regimens between 2015-2019 were included; no neo-adjuvant therapy (NT), neo-adjuvant chemotherapy (CT), neo-adjuvant radiochemotherapy (RCT), neo-adjuvant radiotherapy with a long interval (LRT) or short interval (SRT). In order to minimize heterogeneity we excluded cT1 tumors, cT4 tumors as well as stage IV rectal cancers. Consecutive slides were stained for HE, LC3-II (autophagy stain) and a multiplex immunofluorescence VECTRA panel for CD8, CD3, CD20, Foxp3, CD11c and pan-CK AE 1/3. Tumor response was scored by two independent investigators.
Results: A total of 80 rectal cancer patients were included. Median age was slightly biased, with older patients in the SRT groups and younger patients in the CT group (p=0.03). Less regression and more lymph-node involvement was seen among the CT group, while higher angioinvasion and lymph node involvement was seen in the SRT group. A fragmented pattern of response was more prevalent in CT and RCT treated patients (&gt;73% of cases), whereas a shrinkage pattern of response was predominant in RTL treated patients (64% of cases). Furthermore, autophagic activity in tumor cells was increased in RCT treated patients, especially compared to NT and CT. When analyzing the tumor immunophenotype, differences were found according to specific treatment regimens. RCT treated patients seemed to have lower stromal CD4+ cells, Foxp3+ cells and CD11c+ cells. The latter were found to be especially decreased in treatments will longer intervals (CT, RCT, LTR) compared to those with no treatment or immediate surgery (NT and SRT). The specific relations within the network of immune cells and how these relate to autophagy and the patterns of response are currently being evaluated. Thus, further results will follow shortly.
Conclusions: We demonstrated treatment-specific differences in the immune microenvironment landscape of rectal cancer patients. We found higher autophagic activity in patients who received RT treatment, especially significant in the RCT group. Lower immune cell density was observed in longer wait intervals, stressing the importance of immune recovery. Understanding the immune landscape after a specific therapy will shed light on to future treatment decisions, as using immunotherapy in combination with established treatments is the future of personalized therapy.
Citation Format: Cristina Graham Martinez, Yari F. H. C. Barella, Sonay Kus Öztürk, Mark A. Gorris, Corrie A. Marijnen, Iris D. Nagtegaal. Immune microenvironment landscape shows treatment-specific differences in rectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2549.