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

Eric M. Letessier, Dae Seog Heo, Thomas Okarma, Jonas T. Johnson, Ronald B. Herberman, Theresa L. Whiteside

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Abstract

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. CDS+ 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 CDS+ 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+CDllb- 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 CDS+ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CDS+ 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.

Original languageEnglish
Pages (from-to)3891-3899
Number of pages9
JournalCancer Research
Volume51
Issue number15
StatePublished - 1 Aug 1991

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CD8-Positive T-Lymphocytes
Head and Neck Neoplasms
Lymph Nodes
Lymphocytes
Neoplasms
T-Lymphocytes
Feeder Cells
Antibodies
T-Lymphoid Precursor Cells

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Letessier, E. M., Heo, D. S., Okarma, T., Johnson, J. T., Herberman, R. B., & Whiteside, T. L. (1991). Enrichment in Tumor-reactive CD8+ T-Lymphocytes by Positive Selection from the Blood and Lymph Nodes of Patients with Head and Neck Cancer. Cancer Research, 51(15), 3891-3899.
Letessier, Eric M. ; Heo, Dae Seog ; Okarma, Thomas ; Johnson, Jonas T. ; Herberman, Ronald B. ; Whiteside, Theresa L. / Enrichment in Tumor-reactive CD8+ T-Lymphocytes by Positive Selection from the Blood and Lymph Nodes of Patients with Head and Neck Cancer. In: Cancer Research. 1991 ; Vol. 51, No. 15. pp. 3891-3899.
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Letessier, EM, Heo, DS, Okarma, T, Johnson, JT, Herberman, RB & Whiteside, TL 1991, 'Enrichment in Tumor-reactive CD8+ T-Lymphocytes by Positive Selection from the Blood and Lymph Nodes of Patients with Head and Neck Cancer', Cancer Research, vol. 51, no. 15, pp. 3891-3899.

Enrichment in Tumor-reactive CD8+ T-Lymphocytes by Positive Selection from the Blood and Lymph Nodes of Patients with Head and Neck Cancer. / Letessier, Eric M.; Heo, Dae Seog; Okarma, Thomas; Johnson, Jonas T.; Herberman, Ronald B.; Whiteside, Theresa L.

In: Cancer Research, Vol. 51, No. 15, 01.08.1991, p. 3891-3899.

Research output: Contribution to journalArticle

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T1 - Enrichment in Tumor-reactive CD8+ T-Lymphocytes by Positive Selection from the Blood and Lymph Nodes of Patients with Head and Neck Cancer

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AU - Heo, Dae Seog

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AU - Johnson, Jonas T.

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AU - Whiteside, Theresa L.

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AB - 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. CDS+ 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 CDS+ 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+CDllb- 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 CDS+ PBLs did not result in improved proliferation or antitumor function of the effector cells. Positive selection on antibody-coated flasks of CDS+ 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.

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