CD58/LFA-3 and IL-12 provided by activated monocytes are critical in the in vitro expansion of CD56(+) T cells
Division of Blood and Marrow Transplantation, Stanford University, Palo Alto, California, United States Cancer Immunology and Immunotherapy
(Impact Factor: 3.94).
03/2001; 49(12):629-40. DOI: 10.1007/s002620000148
A small proportion of human CD3+ T lymphocytes are known to co-express CD56, an antigen usually restricted in its expression to natural killer (NK) cells. Whereas the in vivo function of CD3+ CD56+ T cells remains unknown, we and others have previously shown that both in vitro and in vivo, these cells can mediate a significantly greater degree of MHC-unrestricted cytotoxicitv against a variety of human tumor cells when compared to either CD3+ CD56- T cells or lymphokine activated killer (LAK) cells. While the mechanismns regulating the in vivo expansion of CD56+ T cells are not known, here we demonstrate the importance of CD2-mediated IL-12-dependent signals in the in vitro expansion of CD56+ T cells. Specifically, we show that activated monocytes provide a contact dependent factor (CD58/LFA-3) and a soluble factor (IL-12), both critical for the in vitro expansion of CD56+ T cells. The biological and therapeutic implications of these findings are discussed.
Available from: Sebastian Rogenhofer
- "Most of these CIK cells (87%) are positive for CD3 and for one of the T-cell coreceptor molecules CD4 (37.4%) or CD8 (64.2%), respectively. IFN-γ, added at day 0, activates monocytes providing crucial signals to T cells via interleukin-12 (IL-12) and CD58 (LFA-3) to expand CD56+ cells . After 14 days of culture, 37.7% of cells are CD3+CD8+CD56+. "
[Show abstract] [Hide abstract]
ABSTRACT: Metastatic renal cell carcinoma (RCC) seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK) cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable.
studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.
Available from: PubMed Central
- "At the end of the culture, the CD3 + CD56 + cells, derived from CD3 + CD56 − cells, could expand by up to 1000-fold and gave the greatest cytotoxicity against various tumor cell targets, including K562 and B cell lymphoma cell lines, as compared to CD3 + CD56 − cells . The expression of CD56 on these non-MHC-restricted effector T cells was found to be the result of IFN-γ-priming that induced the production of IL-12 by monocytes and the upregulation of CD58 (LFA- 3), both of which were demonstrated to be crucial for the expansion of CD56 + T cells . Subsequently, this unique subset of non-MHC-restricted CD3 + CD56 + T cells was referred to as NK-like T cells since, similar to the NK cells, they do not require prior specific sensitization to induce the recognition of target cells. "
[Show abstract] [Hide abstract]
ABSTRACT: Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.