Seoul National University Boramae Medical Center, Seoul, Korea, Republic of (South)
Seung Chul Heo, Jie-Eun Kim, Rumi Shin
Background: Immunoediting other than PD-1 works in colorectal cancer (CRC), except for some MSI high tumors. Study of immune response to cancers in the primary CRC is difficult due to interference by the colonic microorganisms. If a clinical model reflecting tumor progression, free from microbial antigens and characterizing the microenvironment is developed it will help us understand the immunoediting of CRC. We studied immunologic changes, according to the peritoneal tumor progression, in ascites and peritoneal immune cells of CRC patients. These results will provide clues to the immunoediting of CRC and to immunotherapy of peritoneal carcinomatosis. Methods: Ascites and peritoneal cells were collected from CRCs during surgery or malignant ascites drainage. Forty-two immune molecules and ratios of immune cells were assayed. Patients with intestinal perforation or leukocytosis were excluded to remove interference by the foreign antigens. Patients were grouped according to the peritoneal tumor progression (PC stages) as follows; SE-: without peritoneal exposure of cancer cells (T3 or lower T stage, no tumor cells in peritoneal cavity); SE+: with peritoneal exposure without peritoneal seeding (T4, microscopic tumor cells in peritoneal cavity); l-PC: localized peritoneal seeding; g-PC: generalized peritoneal seeding. Molecular and cellular changes were evaluated according to PC stages. Results: Of the 42, five (IL-10, IL-6, VEGF, CCL20 and TGF-b) increased with the PC stage progression, meanwhile IL-18 decreased. CXCL8 was elevated in only g-PC. However, 14 molecules could not be assayed due to lower level than the references and other 3 could be assayed in only some g-PCs. The other 18 were not different among PC stages. Especially, IL-10 is a prognostic factor of peritoneal recurrence in SE+. IL-10 and IL-6 are highly correlated. The ratio of CD56+ cells, but not the others, increased according to PC stages. Conclusions: Intraperitoneal CRC growth accompanied IL-10, IL-6, VEGF, CCL20, TGF-b and NK cell increase, meanwhile IL-18 decrease. IL-10 is a prognostic factor of peritoneal recurrence. Identification of secreting and targeting cells of each molecules as well as immune network will provide the clues to immunoediting of CRC.
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