title: Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.
abstract: Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gabrielson
authors.affiliation: First Hospital of Hunan University of Chinese Medicine, Changsha City, Hunan Province, People's Republic of China.
authors.forename: Yunan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Hongkun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Jiji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kallakury
authors.affiliation: Caris Life Science, Irving, Texas.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gatalica
authors.affiliation: Caris Life Science, Irving, Texas.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Kleiner
authors.affiliation: Medstar Transplant Institute, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fishbein
authors.affiliation: Department of Surgery, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Lynt
authors.initials: L
authors.lastname: Johnson
authors.affiliation: Medstar Transplant Institute, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Eddie
authors.initials: E
authors.lastname: Island
authors.affiliation: Medstar Transplant Institute, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Rohit
authors.initials: R
authors.lastname: Satoskar
authors.affiliation: Department of Radiology, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Filip
authors.initials: F
authors.lastname: Banovac
authors.affiliation: Department of Radiology, Georgetown University Hospital, Washington, District of Columbia.
authors.forename: Reena
authors.initials: R
authors.lastname: Jha
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Jaydeep
authors.initials: J
authors.lastname: Kachhela
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Perry
authors.initials: P
authors.lastname: Feng
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Tiger
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Anteneh
authors.initials: A
authors.lastname: Tesfaye
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Petra
authors.initials: P
authors.lastname: Prins
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Loffredo
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Louis
authors.initials: L
authors.lastname: Weiner
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
authors.forename: Michael
authors.initials: M
authors.lastname: Atkins
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia. arh29@georgetown.edu.
authors.forename: Aiwu Ruth
authors.initials: AR
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D017252:CD3 Complex; D009363:Neoplasm Proteins