ALL STEM CELLS

Natural killer cell lines kill autologous b2-microglobulin-deficient melanoma cells: Implications for cancer immunotherapy 1997

ABSTRACT Cancer vaccines used to generate specific cytotoxic T lymphocytes are not effective against tumor cells that have lost or suppressed expression of their class I major histocompatibility complex proteins. This loss is common in some cancers and particularly in metastatic lesions. We show
that b2-microglobulin-deficient class I-negative melanoma variants derived from patients undergoing specific T cell therapy are lysed by heterologous as well as autologous natural killer (NK) lines and clones, but not by specific T cells.
Moreover, the minor NK cell fraction but not the major T cell fraction derived from heterologous lymphokine activated killer cells kills those tumor cell lines. ICAM-1 expression by the different class I protein deficient tumors was correlated with their sensitivity to lysis by NK cells. Adoptive autologous NK therapy may be an important supplement to consider in the design of new cancer immunotherapies.

In the last decade, the field of cancer immunotherapy based on tumor-specific vaccines and antitumor-specific cytotoxic T lymphocytes (CTL) has advanced rapidly (reviewed in refs. 1–3).
However, whether adoptive therapy with T cells or peptide-based vaccines to generate T cells is employed, the obstacle of major histocompatibility complex (MHC)-negative tumor variants still
poses a problem for current experimental protocols in cancer therapy.

 

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