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World J Methodol. Jan 20, 2022; 12(1): 43-53
Published online Jan 20, 2022. doi: 10.5662/wjm.v12.i1.43
Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer
Katerina Kampoli, Periklis G Foukas, Anastasios Ntavatzikos, Nikolaos Arkadopoulos, Anna Koumarianou
Katerina Kampoli, Anastasios Ntavatzikos, Anna Koumarianou, Hematology Oncology Unit, The Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
Periklis G Foukas, The Second Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
Nikolaos Arkadopoulos, The Fourth Surgical Clinic, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
Author contributions: Foukas PG and Koumarianou A designed the research; Kampoli K and Ntavatzikos A performed the bibliographic research and drafted the manuscript; Arkadopoulos N, Foukas P and Koumarianou A critically revised the manuscript for important intellectual content.
Conflict-of-interest statement: All authors declare no conflicts-of interest related to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anna Koumarianou, MD, Hematology Oncology Unit, The Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 1st Rimini Street, Haidari 12462, Athens, Greece. akoumari@yahoo.com
Received: May 30, 2021
Peer-review started: May 30, 2021
First decision: July 31, 2021
Revised: August 17, 2021
Accepted: December 28, 2021
Article in press: December 28, 2021
Published online: January 20, 2022
Processing time: 231 Days and 17.8 Hours
Abstract

Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide. At the time of diagnosis, more than 20% of patients already have metastatic disease. In the last 20 years, the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor, anti-BRAF and antiangiogenics. Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow, proliferate and metastasize. Many molecules are involved in this proangiogenic process, such as vascular endothelial growth factor and its receptors on endothelial cells. A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31, CD34 and CD105 antigens. Even smaller molecules, such as the microRNAs, which are small non-coding RNAs, are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis. In this review, we will discuss recent advances regarding the investigation of angiogenesis, the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+ T cells in the tumor bed. Furthermore, we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.

Keywords: Vascular endothelial growth factor; Circulating tumor cells; Colorectal cancer; MicroRNAs; Microvascular density; Crosstalk; Angiogenesis; Immunity

Core Tip: Colon cancer is one of the most common malignancies with a poor prognosis in patients with metastatic disease. Because of the need to find more effective treatments, researchers are focusing on deciphering the mechanisms used by the cancer cell for survival, food and metastasis. The main events in this process are neoangiogenesis and immune escape through the interplay of growth factors involved in both pathways. This review presents the events involved in these pathways with a focus on their prognostic and predictive value.