title: In situanalysis of FOXP3+regulatory T cells and myeloid dendritic cells in human colorectal cancer tissue and tumor-draining lymph node.
abstract: Forkhead box protein 3 (FOXP3) regulatory T cells (Tregs) are important in the maintenance of tumor immunity tolerance. Myeloid dendritic cells (mDCs) are antigen-presenting cells (APCs) specialized to initiate and regulate immunity. Tregs and mDCs are suspected of influencing the interaction between the tumor and immune system, and thus the course of tumors. However, the implication and interaction of their concurrent infitration in colorectal cancer (CRC) remain unknown. The aim of this study was to determine FOXP3+Tregs and CD11c+mDCs infiltration in CRC and tumor-draining lymph node (TDLN) and to explore the clinical and pathological implication of suppressor and effector immune cell subsets. Immunohistochemical assay was conducted to assess FOXP3+Tregs and CD11c+mDCs infiltration in tumor tissue and in metastasis-free TDLN (mfTDLN) and metastatic TDLN (mTDLN). The results showed that FOXP3+Tregs and CD11c+mDCs infiltration was higher in tumor tissue compared to adjacent normal mucosa (P<0.001). FOXP3+Tregs infiltration was associated with advanced tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.001 and P<0.001, for TNM stage and lymph node metastasis, respectively), whereas less CD11c+mDCs infiltration of tumorin situwas associated with deeper tumor invasion, advanced TNM stages and lymph node metastasis (P<0.05, P<0.001 and P<0.001, for tumor invasion depth, TNM stages and lymph node metastasis, respectively). Compared to mfTDLN, mTDLN was significantly enriched in FOXP3+Tregs (P<0.001) and reduced in CD11c+mDCs (P<0.001). The statistical analysis demonstrated no significant correlations in Tregs and mDCs infiltration. These results suggest that more FOXP3+Tregs and less CD11c+mDCs infiltration have stronger prognostic significance in CRC. The presence of tumor cells in mTDLN may contribute to a tolerogenic milieu and facilitate the survival of metastatic tumor cells.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin 132013;
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Gai
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin 132013;
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin 132013;
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pathology, The General Hospital of CNPC in Jilin, Jilin 132022;
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Lei
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Peking University and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, P.R. China.
authors.forename: Bao-Xue
authors.initials: BX
authors.lastname: Yang
keywords: colorectal cancer; immune state; myeloid dendritic cells; regulatory T cells; tumor metastasis; tumor-draining lymph nodes