{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:48:16Z","timestamp":1791654496406,"version":"4.3.4"},"reference-count":278,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) remains the leading cause of morbidity and mortality for both men and women worldwide. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME) of solid tumors, including CRC. These macrophages are found in the pro-inflammatory M1 and anti-inflammatory M2 forms, with the latter increasingly recognized for its tumor-promoting phenotypes. Many signaling molecules and pathways, including AMPK, EGFR, STAT3\/6, mTOR, NF-\u03baB, MAPK\/ERK, and HIFs, are involved in regulating TAM polarization. Consequently, researchers are investigating several potential predictive and prognostic markers, and novel TAM-based therapeutic targets, especially in combination therapies for CRC. Macrophages of the gastrointestinal tract, including the normal colon and rectum, produce growth hormone-releasing inhibitory peptide\/somatostatin (SRIF\/SST) and five SST receptors (SSTRs, SST1-5). While the immunosuppressive function of the SRIF system is primarily known for various tissues, its role within CRC-associated TAMs remains underexplored. This review focuses on the following three aspects of TAMs: first, the role of macrophages in the normal colon and rectum within the broader context of macrophage biology; second, the various bioactive factors and signaling pathways associated with TAM function, along with potential strategies targeting TAMs in CRC; and third, the interaction between the SRIF system and macrophages in both normal tissues and the CRC microenvironment.<\/jats:p>","DOI":"10.3390\/ijms26115336","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Regulation and Function of Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): The Role of the SRIF System in Macrophage Regulation"],"prefix":"10.3390","volume":"26","author":[{"given":"Agnieszka","family":"Geltz","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, Swiecicki Street 6, 60-781 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, Bukowska Street 70, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8033-9386","authenticated-orcid":false,"given":"Jakub","family":"Geltz","sequence":"additional","affiliation":[{"name":"Doctoral School, Poznan University of Medical Sciences, Bukowska Street 70, 60-812 Poznan, Poland"},{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Street 27\/33, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-3038","authenticated-orcid":false,"given":"Aldona","family":"Kasprzak","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Poznan University of Medical Sciences, Swiecicki Street 6, 60-781 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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