Abstract
Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cells (Tregs) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. A cancer progression gene array analysis and Immunohistochemical analysis of FOXP3 as Treg marker, CD8 as Tumor-infiltrating lymphocyte marker, and CXCR4 expression on activate Treg was also examined in a series of 31 conjunctival SCC cases. To investigate the localization of FOXP3-positive Tregs in detail, the tumor surface, tumor central, and around vessels staining patterns of FOXP3, CD8, and CXCR4 were examined separately. A significant difference in FOXP3, CD8, and CXCR4 staining in tumor-infiltrating lymphocytes and FOXP3/CD8 ratio were in the carcinoma in situ group than advanced stage SCC group(each P < 0.01). In addition, FOXP3/CD8 ratio was correlation with progression-free survival. Double immunostaining of CXCR4/FOXP3 correlate with American Joint Committee on Cancer T-stage, independent of age or Ki67 index(P༜0.01). Our results show that FOXP3, the FOXP3/CD8 ratio, and the CXCR4 axis are important pathologic and prognostic factors of ocular surface neoplasia, including SCC. These tumor microenvironment of conjunctival SCC may be considered in the future development of treatment options.