Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1988;26(1):1-10.
doi: 10.1007/BF00199840.

Cytolytic antitumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes in recombinant interleukin 2

T L Whiteside  1 , D S Heo, S Takagi, J T Johnson, S Iwatsuki, R B Herberman
Affiliations

Cytolytic antitumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes in recombinant interleukin 2

T L Whiteside et al. Cancer Immunol Immunother. 1988.

Abstract

Lymphocytes infiltrating human solid tumors (TIL) and autologous peripheral blood lymphocytes (A-PBL) were cultured with 1000 units/ml of recombinant interleukin 2 (rIL2) in long-term cultures. TIL isolated from 26 primary squamous cell carcinomas of the head and neck expanded better (P less than 0.01) and achieved higher total lytic units of activity against fresh tumor cell targets (P less than 0.05) than A-PBL. TIL obtained from primary hepatocellular carcinomas (n = 7) showed a higher degree of expansion than those from metastatic liver tumors (n = 7). Further, TIL from metastatic tumors of the head and neck, liver, and ovary were delayed up to 50 days in their proliferative response to rIL2. Long-term mass cultures in rIL2 of TIL, A-PBL, or normal PBL were serially monitored for cytotoxicity with different cultured and fresh tumor cell targets and for phenotypic markers of the predominating cell populations. Antitumor cytotoxicity was found in cultures enriched in CD3+Leu19+ and/or CD3-Leu19+ cells. Two-color sorting of such cultures followed by cytotoxicity assays confirmed that the human antitumor effectors expressed either the CD3+Leu19+ or CD3-Leu19+ phenotype. CD3+Leu19- cells had little or no antitumor cytotoxicity. The two types of Leu19+ effector cells were present in low numbers in fresh TIL, A-PBL, or normal PBL; in contrast, in some rIL2-expanded long-term cultures, they represented a majority of proliferating cells. This study identifies for the first time two types of antitumor effector cells in rIL2 cultures of human TIL, one of which may represent activated natural killer cells on the basis of the absence of the CD3 and expression of the Leu19 antigen. These antitumor effector cells mediate non-MHC-restricted cytotoxicity of fresh or cultured tumor cell targets of different histologic types.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Brunner KT, MacDonald HR, Cerottini J-C. Quantitation and clonal isolation of cytotoxic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors. J Exp Med. 1981;154:362–373. - PMC - PubMed
    1. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon. Lysis of natural killer resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982;155:1823–1841. doi: 10.1084/jem.155.6.1823. - DOI - PMC - PubMed
    1. Heo DS, Whiteside TL, Johnson JT, Chen K, Barnes EL, Herberman RB (1987) Long-term interleukin 2-dependent growth and cytotoxic activity of tumor-infiltrating lymphocytes (TIL) from human squamous cell carcinomas of the head and neck. Cancer Res (in press) - PubMed
    1. Hutchinson GH, Heinemann D, Symes MO, Williamson RCN. Differential immune reactivity of tumor-intrinsic and peripheral blood lymphocytes against colorectal carcinoma cells. Br J Cancer. 1981;44:396–402. - PMC - PubMed
    1. Kurnick JT, Kradin RL, Blumberg R, Schneeberger EE, Boyle LA. Functional characterization of T lymphocytes propagated from human lung carcinomas. Clin Immunol Immunopathol. 1986;38:367–380. - PubMed

LinkOut - more resources