title: HLA class I antigen expression is associated with a favorable prognosis in early stage non-small cell lung cancer.
abstract: Human leukocyte antigen (HLA) class I displays a repertoire of endogenously processed peptides to CD8(+) T lymphocytes. The present study assessed correlations between HLA class I expression, clinicopathologic factors, and tumor-infiltrating immune cells in human non-small cell lung cancers (NSCLC). Expression of HLA class I was assessed in 161 resected primary NSCLC by immunohistochemistry using EMR8-5, a novel monoclonal anti-pan HLA class I heavy chain antibody. Expression of HLA class I was classified into three categories: strongly positive, weakly positive, or negative. Tumor-infiltrating CD8(+) lymphocytes and CD56(+) natural killer cells within cancer nests and stroma were also counted. Expression of HLA class I was strongly positive in 50 tumors, weakly positive in 57 tumors, and negative in 54 tumors. Down-regulation of HLA class I was significantly correlated with male sex, history of smoking, non-adenocarcinoma histology, and moderate-/low-grade differentiation. The density of cancer nest-infiltrating CD8(+) cells in HLA class I-negative tumors was significantly decreased compared to that in HLA class I strongly positive tumors (P < 0.01). Kaplan-Meier analysis revealed a significant favorable influence on overall survival for patients displaying tumors with strongly positive expression of HLA class I (P < 0.01). Multivariate analysis revealed down-regulation of HLA class I as an independent factor of poor prognosis in pathological stage I patients, but not in late-stage patients. These results suggest that down-regulation of HLA class I expression in NSCLC is a marker of poor prognosis, and this may play a critical role in immune surveillance of patients with NSCLC.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kitaku, Sapporo 060-8638, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Cho
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Hommura
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin