Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer.
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.
Coleman
Sharon
S
Department of Oncology and Palliative Medicine, Velindre Hospital, Whitchurch, Cardiff, UK.
Clayton
Aled
A
Mason
Malcolm D
MD
Jasani
Bharat
B
Adams
Malcolm
M
Tabi
Zsuzsanna
Z
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
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