title: Correlation of tumor-infiltrative lymphocyte subtypes alteration with neoangiogenesis before and after neoadjuvant chemotherapy treatment in breast cancer patients.
abstract: The two most important factors in tumor-stromal interactions are tumor-infiltrating lymphocytes (TIL) and neoangiogenesis (NAng). While changes of these parameters in responders of neoadjuvant chemotherapy (NCTx) have been reported, their correlation with pathological response in breast cancer (BC) patients treated with NCTx have not been described. We therefore evaluated alterations of the TIL subtypes ratio and alterations of NAng using the vasohibin-1-positive ratio (VPR) in BC patients during the course of NCTx. To this aim we used: (i) double immunohistochemistry of CD8 cytotoxic T cells and T regulatory cells (Treg) with Foxp3, determining the CD8+/Foxp3 ratio; (ii) immunostaining of CD31 and vasohibin-1, yielding the VPR, which reflects the NAng status. Changes between the CD8+/Foxp3 ratio and VPR before and after therapy were then correlated with the pathological response of the patients. A concomitant significant decrement of Foxp3 and NAng, represented by VPR, were detected only in NCTx pathological responders (p<0.001 and p=0.044, respectively). The CD8+/Foxp3 ratio increased in both responders and non-responders, but to greater extent in responders (p=0.02). The changes of VPR in the NCTx-treated group differed from those recorded for the patients treated with aromatase inhibitors and shown in our earlier study; this indicates that the reactions of the tumor-stromal interaction to therapy were different among different treatments in BC patients. Changes in Foxp3 and VPR in responders may reflect the dynamic activity of tumor stroma and host immune response to tumor antigens in the tumor microenvironment in response to the NCTx. VPR can be a potential surrogate marker in BC specimens for predicting the response to NCTx, incorporating both features of carcinoma and stromal cells.
authors.affiliation: Department of Pathology, Tohoku University School of Medicine of Medicine, Sendai - Japan.
authors.forename: Monica S M
authors.initials: MS
authors.lastname: Chan
authors.forename: Shi-Fan
authors.initials: SF
authors.lastname: Chen
authors.forename: Saulo J A
authors.initials: SJ
authors.lastname: Felizola
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Noriko
authors.initials: N
authors.lastname: Nemoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.forename: Louis W C
authors.initials: LW
authors.lastname: Chow
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000276:immunology; D001943:Breast Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply* / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D020360:Neoadjuvant Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D017154:Stromal Cells / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D043823:Taxoids / Q000008:administration & dosage; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil