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Recovery of CD8⁺ T-Cell Function During Systemic Chemotherapy in Advanced Ovarian Cancer

¹ Department of Oncology and Palliative Medicine, Velindre Hospital, Whitchurch and ² Department of Pathology, Heath Park, Cardiff, School of Medicine, Cardiff University; and ³ Velindre NHS Trust, Whitchurch, Cardiff, United Kingdom

Requests for reprints: Zsuzsanna Tabi, Department of Clinical Oncology and Palliative Medicine, School of Medicine, Cardiff University, Velindre Hospital, Whitchurch, Cardiff CF14 2TL, United Kingdom. Phone: 44-29-20-196-137; Fax: 44-29-20-529-625; E-mail: Zsuzsanna.Tabi{at}velindre-tr.wales.nhs.uk.

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.

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