title: Prognostic significance of programmed cell death-1-positive cells in follicular lymphoma patients may alter in the rituximab era.
abstract: Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T-cell responses and promotion of T-cell tolerance. PD-1 is known to negatively regulate T-cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at six institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1-positive cells.
authors: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors: Hiroyuki
authors: H
authors: Takahashi
authors: Naoto
authors: N
authors: Tomita
authors: Seiji
authors: S
authors: Sakata
authors: Naoko
authors: N
authors: Tsuyama
authors: Chizuko
authors: C
authors: Hashimoto
authors: Rika
authors: R
authors: Ohshima
authors: Shiro
authors: S
authors: Matsuura
authors: Koji
authors: K
authors: Ogawa
authors: Wataru
authors: W
authors: Yamamoto
authors: Yoichi
authors: Y
authors: Kameda
authors: Makiko
authors: M
authors: Enaka
authors: Yoshiaki
authors: Y
authors: Inayama
authors: Masao
authors: M
authors: Kasahara
authors: Yoshinori
authors: Y
authors: Takekawa
authors: Noboru
authors: N
authors: Onoda
authors: Shigeki
authors: S
authors: Motomura
authors: Yoshiaki
authors: Y
authors: Ishigatsubo
authors: Kengo
authors: K
authors: Takeuchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012189:Retrospective Studies; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C571759:R-CHOP protocol; D001613:beta 2-Microglobulin; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone