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Enrichment in Tumor-reactive CD8⁺ T-Lymphocytes by Positive Selection from the Blood and Lymph Nodes of Patients with Head and Neck Cancer¹

Departments of Pathology [E. M. L., D. S. H., R. B. H., T. L. W.], Otolaryngology [J. T. J.], and Medicine [R. B. H.], University of Pittsburgh School of Medicine, and Pittsburgh Cancer Institute [E. M. L., D. S. H., J. T. J., R. B. H., T. L. W.], Pittsburgh, Pennsylvania 15213, and Applied Immune Sciences, Menlo Park, California 94025 [T. O.]

To study antitumor functions of T-lymphocyte subpopulations in the blood [peripheral blood lymphocytes (PBLs)] and tumor-draining lymph nodes (LNs) of patients (n = 26) with squamous cell carcinoma of the head and neck (SCCHN), antibody-coated devices were used to positively select CD8⁺ or CD4⁺ cells. The mean percentage of CD8⁺ cells captured on antibody-coated flasks from PBLs was 92% and that captured from lymph node lymphocytes (LNLs) was 98%. The initial enrichment in CD4⁺ T-cells was comparable. CD8⁺ T-lymphocytes captured from PBLs proliferated as well as unseparated lymphocytes in both patients with SCCHN and normal donors, while captured CD4⁺ PBLs of the patients showed significantly lower expansion than those of normal volunteers. Unseparated LNLs proliferated as well as PBLs, but captured CD4⁺ or CD8⁺ LNLs failed to proliferate in the presence of interleukin 2 (100 units/ml) and phytohemagglutinin (5 µg/ml). The addition to captured LNL cultures of irradiated autologous or allogeneic feeder cells significantly improved expansion of CD8⁺ LNLs but not CD4⁺ LNLs. During 15-day culture of captured CD8⁺ PBLs or CD8⁺ LNLs in the presence of feeder cells, a significant (P < 0.05) enrichment in CD8⁺ T-cells was maintained [94 ± 5% (mean ± SEM) or 99.5 ± 0.1%, respectively, on day 15]. Capture of CD8⁺ LNLs and their expansion resulted in the outgrowth of CD8⁺CD11b^- effectors which had no or little cytotoxicity against Daudi, low cytotoxicity against K562, and very high levels of cytotoxicity against 4 different natural killer cell-resistant SCCHN targets, as measured in 4-h ⁵¹Cr release assays. Such significant enrichment in SCCHN-restricted cytotoxicity could be obtained with LNLs from tumor-uninvolved LNs but not from tumor-involved LNs. Captured and cultured CD4⁺ LNLs had no preferential anti-SCCHN cytotoxicity. The addition of irradiated autologous tumor cells to captured CD8⁺ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CD8⁺ T-lymphocytes from tumor-uninvolved LNs of patients with SCCHN led to the enrichment in SCCHN-restricted but the major histocompatibility complex-unrestricted effector cells in 15-day cultures. Thus, CD8⁺ lymphocytes separated from tumor-draining LNs in patients with head and neck cancer contained cytolytic T-cell precursors capable of developing into effectors with preferential activity against SCCHN targets.

¹ Supported in part by NIH Grant 1PO1-CA4744501A2 and American Cancer Society Grant IM588A (to T. L. W.). E. M. L. was supported by Association pour le Recherche sur le Cancer, 94801, Villejuif, France.

² To whom requests for reprints should be addressed, at Pittsburgh Cancer Institute, Room W1041, Biomedical Science Tower, DeSoto at O'Hara Street, Pittsburgh, PA 15213.

Received 2/26/91. Accepted 5/15/91.

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