Restoration of the immunocompetence by IL-2 activation and tcr-cd3 engagement of the in vivo anergized tumor-specific CTL from lung cancer patients

Yuh Min Chen, Wen Kuang Yang, Jacqueline Whang-Peng, Wen Ying Tsai, Yi Mei Hung, Den Mei Yang, Wen Chang Lin, Reury Perng Perng, Chou Chik Ting

Research output: Contribution to journalArticle

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Abstract

The present study investigates the nature of the immunosuppressed state of the lymphocytes obtained from the malignant pleural effusion (effusion associated lymphocytes, EAL) of lung cancer patients. The immunocompetence of EAL from 13 patients was assessed by determining their T-helper cell phenotype, proliferative response to αCD3-activation, and their cytolytic activity against three tumor targets: the autologous tumor, Daudi, and K562. Flow cytometry analysis showed that the lymphocytes in EAL were predominantly T cells with < 1% natural killer cells. The T-helper cell phenotype was found to be predominantly of Th2 type, but could be readily converted to Thl type by culturing the EAL in vitro, and this conversion was augmented by interleukin-2 (IL-2) or IL-2 plus αCD3. To test the cytolytic activity of EAL, it was found that after 6-day culturing, the EAL remained in an immunosuppressed state so that they failed to kill any of the three tumor targets. Stimulation with IL-2 partially restored the immunocompetence of EAL. Further engagement of TCR-CD3 by αCD3 fully restored the cytolytic activity of the EAL to kill the autologous tumor target but not Daudi or K562 tumor cells, and thus seemed to be tumor specific. The specificity was further confirmed by testing the activated EAL and normal donor peripheral blood lymphocytes against a variety of tumor targets and control targets. Furthermore, the killing by EAL against the autologous tumor target seemed to be major histocompatibility complex-restricted and was inhibited by anti-human leukocyte antigen class I antibody. The EAL from lung cancer patients also showed much reduced responsiveness to the αCD3 stimulation to induce proliferation, and addition of IL-2 restored the responsiveness. These results suggest that, through close contact with tumor cells, anergy of cytotoxic T lymphocytes (CTLs) was induced in vivo at a localized site. IL-2 stimulation and TCR-CD3 engagement could reverse the anergic state and restored the full competence of CTLs in EAL to mediate the specific antitumor killing against the autologous tumor. Proper manipulation of EAL may prove useful as a source of anti-tumor effectors for cancer adoptive immunotherapy.

Original languageEnglish
Pages (from-to)354-364
Number of pages11
JournalJournal of Immunotherapy
Volume20
Issue number5
Publication statusPublished - Jan 1 1997
Externally publishedYes

Fingerprint

Immunocompetence
Cytotoxic T-Lymphocytes
Interleukin-2
Lung Neoplasms
Lymphocytes
Neoplasms
Helper-Inducer T-Lymphocytes
Malignant Pleural Effusion
Phenotype
Adoptive Immunotherapy
K562 Cells
Immunoglobulin Isotypes

Keywords

  • Lung cancer
  • Pleural effusion
  • T-cell anergy
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Restoration of the immunocompetence by IL-2 activation and tcr-cd3 engagement of the in vivo anergized tumor-specific CTL from lung cancer patients. / Chen, Yuh Min; Yang, Wen Kuang; Whang-Peng, Jacqueline; Tsai, Wen Ying; Hung, Yi Mei; Yang, Den Mei; Lin, Wen Chang; Perng, Reury Perng; Ting, Chou Chik.

In: Journal of Immunotherapy, Vol. 20, No. 5, 01.01.1997, p. 354-364.

Research output: Contribution to journalArticle

Chen, Yuh Min ; Yang, Wen Kuang ; Whang-Peng, Jacqueline ; Tsai, Wen Ying ; Hung, Yi Mei ; Yang, Den Mei ; Lin, Wen Chang ; Perng, Reury Perng ; Ting, Chou Chik. / Restoration of the immunocompetence by IL-2 activation and tcr-cd3 engagement of the in vivo anergized tumor-specific CTL from lung cancer patients. In: Journal of Immunotherapy. 1997 ; Vol. 20, No. 5. pp. 354-364.
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abstract = "The present study investigates the nature of the immunosuppressed state of the lymphocytes obtained from the malignant pleural effusion (effusion associated lymphocytes, EAL) of lung cancer patients. The immunocompetence of EAL from 13 patients was assessed by determining their T-helper cell phenotype, proliferative response to αCD3-activation, and their cytolytic activity against three tumor targets: the autologous tumor, Daudi, and K562. Flow cytometry analysis showed that the lymphocytes in EAL were predominantly T cells with < 1{\%} natural killer cells. The T-helper cell phenotype was found to be predominantly of Th2 type, but could be readily converted to Thl type by culturing the EAL in vitro, and this conversion was augmented by interleukin-2 (IL-2) or IL-2 plus αCD3. To test the cytolytic activity of EAL, it was found that after 6-day culturing, the EAL remained in an immunosuppressed state so that they failed to kill any of the three tumor targets. Stimulation with IL-2 partially restored the immunocompetence of EAL. Further engagement of TCR-CD3 by αCD3 fully restored the cytolytic activity of the EAL to kill the autologous tumor target but not Daudi or K562 tumor cells, and thus seemed to be tumor specific. The specificity was further confirmed by testing the activated EAL and normal donor peripheral blood lymphocytes against a variety of tumor targets and control targets. Furthermore, the killing by EAL against the autologous tumor target seemed to be major histocompatibility complex-restricted and was inhibited by anti-human leukocyte antigen class I antibody. The EAL from lung cancer patients also showed much reduced responsiveness to the αCD3 stimulation to induce proliferation, and addition of IL-2 restored the responsiveness. These results suggest that, through close contact with tumor cells, anergy of cytotoxic T lymphocytes (CTLs) was induced in vivo at a localized site. IL-2 stimulation and TCR-CD3 engagement could reverse the anergic state and restored the full competence of CTLs in EAL to mediate the specific antitumor killing against the autologous tumor. Proper manipulation of EAL may prove useful as a source of anti-tumor effectors for cancer adoptive immunotherapy.",
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AU - Tsai, Wen Ying

AU - Hung, Yi Mei

AU - Yang, Den Mei

AU - Lin, Wen Chang

AU - Perng, Reury Perng

AU - Ting, Chou Chik

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