title: Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer.
abstract: Immunologic approaches are emerging as new treatment options in several types of cancer. However, whereas the ability of patients to develop potent CD8+ T-cell responses is crucial for efficient antitumor responses, immunocompetence and T-cell function are not tested routinely in patients entering immunotherapy. The objective of our study was to monitor T-cell function in advanced cancer and during chemotherapy. CD8+ T-cell function of 21 patients with advanced ovarian cancer (stages III-IV) was assessed by cytokine flow cytometry following stimulation of 42 PBMC samples with a panel of synthetic viral peptides in vitro, consisting of pan-Caucasian epitopes. CD8+ T-cell responses were significantly lower in patients with high levels (>200 units/mL) of Ca125 (marker of tumor load and progression) than in those with low Ca125 levels (P = 0.0013). In longitudinal studies of nine patients, chemotherapy was associated with decreasing Ca125 levels in seven cases and also with improvement or maintenance of CD8+ T-cell function in seven cases. After the full course of chemotherapy, five of nine patients in remission displayed potent CD8+ T-cell responses, whereas four of nine patients in progression displayed low or decreasing T-cell responses, pointing toward a correlation between T-cell function and clinical response. Our results show for the first time that CD8+ T-cell function is not permanently suppressed in advanced cancer and successful chemotherapy is associated with improved antigen-specific T-cell reactivity. We suggest that functional assays determining T-cell immunocompetence can be valuable tools for optimizing cancer immunotherapy for improved clinical success.
authors.affiliation: Department of Oncology and Palliative Medicine, Velindre Hospital, Whitchurch, Cardiff, UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Coleman
authors.forename: Aled
authors.initials: A
authors.lastname: Clayton
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Bharat
authors.initials: B
authors.lastname: Jasani
authors.forename: Malcolm
authors.initials: M
authors.lastname: Adams
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Tabi
mesh_terms: D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016190:Carboplatin / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D017239:Paclitaxel / Q000008:administration & dosage; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology
chemical_list: D018394:CA-125 Antigen; C515370:CCR7 protein, human; D016207:Cytokines; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin; D016190:Carboplatin; D017493:Leukocyte Common Antigens; D017239:Paclitaxel