Ascitic Il-10 Concentration Is Correlated To Peritoneal Tumor Burden And A Prognostic Factor Of Peritoneal Recurrence In Colon Cancer.

Purpose: Although immune systems response to cancer cells there are few data on the alterations of immune response to the progression of tumors. We performed this study to search the changes of cytokines in ascites during the progression of colon cancer in peritoneal cavity. Methods: Colon cancer patients were divided into four groups according to the progression status and burden of peritoneal carcinomatosis (PC stages). SE-(serosa exposure negative) is a group of patients without exposure of cancer cells to peritoneal cavity (T3 or lower T stage, n=20). SE+(serosa exposure positive) is a group of patients of T4 lesion without peritoneal metastasis (n=20). l-PC represents localized peritoneal carcinomatosis which could be removed entirely during surgery (n=8). g-PC is a group of generalized peritoneal carcinomatosis (n=7). Ascites were acquired at Douglas pouch right after laparotomy during the course of surgical operation. In five of the 7 g-PC patients, who were diagnosed as g-PC by imaging study, ascites were collected during the therapeutic tapping to relieve abdominal distension. If ascites was contaminated by blood the patient was excluded in this study. Cytokines and IDO (indoleamine deoxygenase) activity were assayed and peritoneal recurrence was surveyed. Result: IL-10 and IL-6 were increased according to the progression of PC stages (SE- <”SE+ < l-PC < g-PC) (p=0.000, ANOVA). Mean IL-10 and IL-6 concentrations (pg/ml) were 17.8 and 456 in SE-, 38.0 and 2,186 in SE+, 64.8 and 2,707 in l-PC and 250.7 and 19,722 in g-PC. When compared in adjacent two PC stages, IL-10 concentration was significantly higher in g-PC than in l-PC (p=0.002) and in SE+ than in SE- (p=0.025) but was not different between l-PC and SE+ (p=0.094, t-test). IL-6 as well as IDO activity was significantly higher in g-PC than in other PC stages (t-test). Interestingly, the increase of IL-10 and IL-6 are significantly correlated (r=0.858, p=0.000). However, TGF-beta, IL-17 and IL-2 as well as proinflammatory cytokines (TNF and IFN-gamma) and Th2 cytokines (IL-4, IL-5 and IL-6) had no changes during the progression of peritoneal carcinomatosis. Peritoneal recurrence, after removal of cancer cells exposed to peritoneal cavity (l-PC and SE+), were diagnosed by imaging studies in 6 of 7 l-PC and in 6 of 19 SE+ patients during the follow up period (median 10 months). Mean IL-10 concentration of patients with recurrence was 68.0 and that without recurrence was 28.3 (p=0.028, t-test). The recurrence free survival was inversely correlated to peritoneal IL-10 concentration. (r= -0.473, p=0.015). Conclusion: Peritoneal IL-10 is not only increased in peritoneal metastasis but also correlated to the progression of peritoneal metastasis, while IL-6 and IDO activity were increased only in advanced stage. And ascitic IL-10 is a candidate for the prognostic marker of peritoneal recurrence in colorectal cancers. Citation Format: Hye Seong Ahn, In Sil Choi, Junghan Song, Seung Chul Heo, Ji-Eun Kim. Ascitic IL-10 concentration is correlated to peritoneal tumor burden and a prognostic factor of peritoneal recurrence in colon cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B33.