title: Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients.
abstract: It remains unclear whether the immunologic status of cells in peripheral blood can be used as a prognostic indicator of response to treatment for patients with unresectable metastatic colorectal cancer (MCRC). We therefore investigated the relationship between the pretreatment immunologic status of 40 patients with MCRC who planned to receive the first-line chemotherapy and their progression-free survival. Twenty-five immune cell subsets, including monocytic myeloid-derived suppressor cells (M-MDSC) and effector memory T cells (TEM), were measured by multicolor-flow cytometry. We divided patients into high and low (above and below the median, respectively) groups based on the median value for each immune cell subset and compared progression-free survival of the two groups. Patients with high M-MDSC, low CD4(+) TEM, or low CD8(+) TEM quantities had significantly shorter progression-free survival (P = 0.004, 0.005, and 0.002, respectively). Patients were classified into two prognostic groups based on numbers of adverse factors; having two or three adverse factors (n = 21, 52.5%) was correlated with significantly shorter progression-free survival compared with none or one (n = 19, 47.5%; P < 0.001). The presence of two or three adverse factors was an independent poor prognostic factor for progression-free survival (HR, 9.2; 95% confidence interval, 2.5-34.2; P < 0.001). These results provide evidence that pretreatment peripheral immune status can inform the outcome of patients with MCRC treated with first-line chemotherapy. Cancer Immunol Res; 4(7); 592-9. ©2016 AACR.
authors.affiliation: National Cancer Center Hospital, Tokyo, Japan. Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan. Immunotherapy and Cell Therapy Service, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tada
authors.affiliation: Department of Experimental Therapeutics (ex. Phase I trial center), National Cancer Center Hospital, Tokyo, Japan. Exploratory Oncology Research and Clinical Trial Center, Division of Cancer Immunotherapy, National Cancer Center, Tokyo, Japan.
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Kitano
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Shoji
authors.affiliation: Department of Gastrointestinal Medicine, Tokyo Jikei Medical University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Nagashima
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Honma
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Okita
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.affiliation: National Cancer Center Hospital, Tokyo, Japan. Immunotherapy and Cell Therapy Service, St. Luke's International Hospital, Tokyo, Japan. heiyuji@luke.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Heike
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007109:Immunity; D016130:Immunophenotyping; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis