title: Decreased intratumoral Foxp3 Tregs and increased dendritic cell density by neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.
abstract: Although neoadjuvant chemotherapy (NACT) has been increasingly used to improve the outcome of advanced gastric cancer (GC) for decades, its precise efficacy has been difficult to evaluate yet. Abundant studies have investigated the predictive factors that represent the effect of NACT on advanced GC. In the present study, the intratumoral infiltration of regulatory T cells (Tregs) and dendritic cells (DCs) response to NACT in advanced GC and their correlation with prognosis were evaluated. Infiltration of Tregs (marked by Foxp3) and DCs (marked by S-100) in 102 advanced GC specimens with or without NACT was measured using immunohistochemical method. Intratumoral infiltration of Foxp3 Tregs was significantly lower and DC density was significantly higher in NACT group than that in nNACT group (P=0.007, P=0.002, respectively). Infiltration of Foxp3 Tregs was significantly associated with tumor invasion depth (P<0.001). The DC density was significantly correlated with histopathologic type (P=0.035), invasion depth (P=0.002), TNM stage (P=0.018), and lymph node metastasis (P<0.001). There was no significant difference of patient's OS between NACT and nNACT groups (P=0.452); however, patients treated with NACT had longer OS with lower infiltration of Foxp3 Tregs (P<0.001) and higher infiltration of DCs (P=0.010). Univariate and multivariate analyses indicated that infiltration of Foxp3 Tregs and DCs were independent prognostic factors (P=0.002, P=0.003, respectively). The results demonstrated that NACT could decrease intratumoral Foxp3 Tregs infiltration and increase DCs density, and that infiltration of Foxp3 Tregs and DCs may serve as novel prognostic biomarkers of human GC.
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Ninu
authors.initials: N
authors.lastname: Maskey
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Chunwei
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil
keywords: FOXP3; Neoadjuvant chemotherapy (NACT); S-100; advanced gastric cancer; dendritic cells (DCs); regulatory T cells (Tregs)