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Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy.

ABSTRACT: Milk fat globule-epidermal growth factor factor 8 (MFG-E8) is secreted from macrophages and is known to induce immunological tolerance mediated by regulatory T cells. However, the roles of the MFG-E8 that is expressed by cancer cells have not yet been fully examined. Expression of MFG-E8 was examined using immunohistochemistry in surgical samples from 134 patients with esophageal squamous cell carcinoma. The relationships between MFG-E8 expression levels and clinicopathological factors, including tumor-infiltrating lymphocytes, were evaluated. High MFG-E8 expression was observed in 23.9% of the patients. The patients with tumors highly expressing MFG-E8 had a significantly higher percentage of neoadjuvant chemotherapy (NAC) history (P < .0001) and shorter relapse-free survival (P = 0.012) and overall survival (OS; P = .0047). On subgroup analysis, according to NAC history, patients with high MFG-E8 expression had significantly shorter relapse-free survival (P = .027) and OS (P = .0039) only when they had been treated with NAC. Furthermore, tumors with high MFG-E8 expression had a significantly lower ratio of CD8+ T cells/regulatory T cells in tumor-infiltrating lymphocytes (P = .042) only in the patients treated with NAC, and those with a lower ratio had a shorter OS (P = .026). High MFG-E8 expression was also found to be an independent prognostic factor in multivariate analysis. The abundant MFG-E8 expression in esophageal squamous cell carcinoma might have a negative influence on the long-term survival of patients after chemotherapy by affecting T-cell regulation in the tumor microenvironment.

SUBMITTER: Kanemura T

PROVIDER: S-EPMC6215892 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy.

Kanemura Takashi T Miyata Hiroshi H Makino Tomoki T Tanaka Koji K Sugimura Keijiro K Hamada-Uematsu Mika M Mizote Yu Y Uchida Hiroaki H Miyazaki Yasuhiro Y Takahashi Tsuyoshi T Kurokawa Yukinori Y Yamasaki Makoto M Wada Hisashi H Nakajima Kiyokazu K Takiguchi Shuji S Mori Masaki M Doki Yuichiro Y Tahara Hideaki H

Cancer science 20180922 11

Milk fat globule-epidermal growth factor factor 8 (MFG-E8) is secreted from macrophages and is known to induce immunological tolerance mediated by regulatory T cells. However, the roles of the MFG-E8 that is expressed by cancer cells have not yet been fully examined. Expression of MFG-E8 was examined using immunohistochemistry in surgical samples from 134 patients with esophageal squamous cell carcinoma. The relationships between MFG-E8 expression levels and clinicopathological factors, includin ...[more]

PMID: 30156356

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Project description:Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center.This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test.The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups.This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.

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Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy.

Publications

Immunoregulatory influence of abundant MFG-E8 expression by esophageal cancer treated with chemotherapy.

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