Robert J. Korst, Jeffrey L. Port, Paul C. Lee, Nasser K. Altorki; Cardiothoracic Surgery, Weill Medical College of Cornell University, New York, NY
Objective: CD8+ T lymphocytes are a necessary component of the antitumor, cellular immune response, however, no published data exist regarding the ability of patients with esophageal carcinoma to mount antigen-specific, CD8+ cell-mediated immune responses. Such data are needed prior to initiating active immunotherapy treatment strategies. The goal of this study is to evaluate CD8+ cell quantity and antigen-specific function in the peripheral blood and regional lymph nodes from patients with esophageal carcinoma.Methods: 31 patients with esophageal carcinoma were accrued prospectively with informed consent. At the time of resection, tumor, regional lymph nodes (RLN), peripheral blood (PB), and parietal pleura were obtained for analysis. CD8+ cells were purified from peripheral blood and lymph nodes, while single cell suspensions were created from the tumor and pleura. CD8+ cells were quantified using flow cytometry and then stimulated using either autologous tumor, a standardized peptide pool, phytohemaglutinin (positive control) or pleura (negative control) in an enzyme-linked immunospot (ELISPOT) assay. A positive ELISPOT indicated intact antigen-specific CD8+ T cell-mediated immunity.
Results: 17 patients underwent esophagectomy without neoadjuvant therapy and 14 received neoadjuvant chemotherapy (carboplatin/paclitaxel/celecoxib) prior to resection. CD8+ cell frequencies were significantly greater in the blood of patients who received chemotherapy compared to those who did not (12.6% vs 7.6%; p=0.02). This difference was not appreciated in the RLN (6.4% vs 4.9%; p=0.2). Tumor-specific, reactive CD8+ cells were detected in only 1/31 patients (3.2%). Despite this, the ability of CD8+ cells to react in an antigen-specific fashion to a standardized peptide pool was detected in 17/30 (57%) in the PB and 20/29 (69%) in the RLN, with no difference appreciated in regard to neoadjuvant chemotherapy. These proportions approximate the reactivity seen in the general population to this peptide pool.
Conclusion: Although tumor-specific CD8+ cell activity can only rarely be detected in patients with esophageal carcinoma, antigen-specific CD8+ cell function appears to be intact, even after neoadjuvant chemotherapy. This finding implies that esophageal carcinoma may be targeted with active immunotherapy treatment strategies.
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