title: PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in non-small cell lung cancer.
abstract: PD-1 expression in peripheral blood T-cells has been reported in several kinds of cancers, including lung cancer. However, the relationship between PD-1 expression in peripheral blood T-cells and prognosis after treatment with a cancer vaccine has not been reported. To elucidate this relationship, we analyzed PD-1 expression in the peripheral blood T-cells of patients with non-small cell lung cancer. The blood samples used in this study were obtained from patients enrolled in phase II clinical trials of a personalized peptide vaccine. Seventy-eight samples obtained before and after a single vaccination cycle (consisting of six or eight doses) were subjected to the analysis. PD-1 was expressed on lymphocytes in the majority of samples. The relative contents of PD1(+) CD4(+) T-cells against total lymphocytes before and after the vaccination cycle correlated with overall survival (OS) with a high degree of statistical significance (P < 0.0001 and P = 0.0014). A decrease in PD-1(+) CD8(+) T-cells after one cycle of vaccination also correlated with longer OS (P = 0.032). The IgG response to the non-vaccinated peptides suggested that the epitope spreading seemed to occur more frequently in high-PD-1(+) CD4(+) T-cell groups. Enrichment of CD45RA(-) CCR7(-) effector-memory phenotype cells in PD-1(+) T-cells in PBMCs was also shown. These results suggest that PD-1 expression on the peripheral blood T-cell subsets can become a new prognostic marker in non-small cell lung cancer patients treated with personalized peptide vaccination.
authors.affiliation: Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Waki
authors.forename: Teppei
authors.initials: T
authors.lastname: Yamada
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshiyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Terazaki
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sugawara
authors.forename: Shinzo
authors.initials: S
authors.lastname: Takamori
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma
keywords: Biomarker; PD-1; lung cancer; peptide vaccine; prognosis