Handbook of Targeted Cancer Therapy and Immunotherapy

108 the immune system, including lymphocytes or myeloid cells and fibroblast populations (3). Notably, CAFs play a major role in facilitating cross-talk and remodeling the archi tecture of the tumor and its surrounding stroma (4). This chapter will provide a brief overview on key immunologic features of GI tumors and our current understanding as to the role of various cellular components and soluble factors in this setting. Inflammation Shapes the Immunologic Profile of GI Tumors Given their anatomic origins, a salient feature present among most GI tumors is a close link with inflammatory pathology. There are many examples illustrating this relationship, including connec tions with viral infections and hepatocellular carcinoma, liver fluke infections with cholangiocar cinoma, Crohn’s- and colitis-associated colorectal cancer, and pancreatitis with pancreatic ductal adenocarcinoma (PDAC) (5–8). Furthermore, it is becoming increasingly appreciated that inflam mation in the GI tract occurs concomitantly with alterations in the microbiome that may further impact cancer risk (9–13). Inflammation most certainly brings about dynamic change in GI tissues that are subject to oxidative damage, fibrosis, and an influx of lymphocytes, myeloid cells, and other innate immune cells that essentially render a failed attempt at restoring tissue homeostasis and re pair (14). Together with underlying genomic aberrations in the epithelial cells residing in GI organs, this scenario perpetuates cellular transformation and tumor formation. Cytokines and Chemokines Perpetuate the Inflammatory Nature of GI Tumors The relationship between inflammation and GI malignancy clearly influences cytokine and im mune cell profiles observed in these tumors. Dynamic interplay between cytokine or chemokine mediators is important for shaping the composition of immune cells within GI tumors. Many cytokines and chemokines are present at high levels either systemically in patients with GI tu mors or within the TME. There is a high degree of redundancy in the functional consequences of this cytokine and chemokine dysregulation, which culminates in a suppressed antitumor

Copyright © 2023 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited.