Tumor immunocompetent cells

Further direct proof that retinoid-effected inhibition of tumor growth and lower incidence of tumors is due to stimulation of the immune system rather than by toxic effects of retinoid directly on the tumor was provided by the experiments of Patek et al. (1979). Animals were thymectomized, lethally irradiated, and reconstituted with fetal liver (ATxFL) in order to compromise their humoral and cell-mediated immune system by the elimination of T cells. Under these conditions it was demonstrated that ATxFL mice are not able to suppress the growth of S91 or L33 tumor growth when treated with retinoid. Therefore, for these two tumor models, it seems highly likely that the retinoid effect requires the participation of immunocompetent cells, in particular, T cells. 

The reader is cautioned that this precis merely highlights those immunocompetent cells that are currently believed to participate in immune responses against tumors. Not discussed, are a multitude of regulatory reactions encompassing helper cells, suppressor cells, cooperations among similar and dissimilar cell types, and soluble factors serving as messengers (see Kumar, 1979)... 

Non-Activated Lymphocytes - Non-activated lymphocytes from healthy HLA-ldentical siblings have been harvested and transfused into the other sibling with advanced cancer with the rationale of Increasing the number of immunocompetent cells for the tumor host. It is conceivable that these lymphocytes may have been sensitized in the healthy donor to the same carcinogenic stimulus as was present overtly in the recipient. In any case transfer of l3rmphocytes had no effect on the tumor. Non-specific or specific vitro lymphocyte activation plus active Immunotherapy were suggested for the future. 

Host-resistance assays can be used to assess the overall immunocompetence of the humoral or cell-mediated immune systems of the test animal (host) to fend off infection with pathogenic microbes, or to resist tumorigenesis and metastasis. These assays are performed entirely in vivo and are dependent on all of the various components of the immune system to be functioning properly. Thus, these assays may be considered to be more biologically relevant than in vitro tests that only assess the function of cells from one source and of one type. Since these assays require that the animal be inoculated with a pathogen or exogenous tumor cell, they cannot be performed as part of a general preclinical toxicity assessment, and are thus classified as Type 2 tests in the revised Redbook. These assays are also included as Tier II tests by the NTP. 

Superficial basal cell carcinoma (sBCC) For the topical treatment of biopsy-confirmed, primary sBCC in immunocompetent adults, with a maximum tumor diameter of 2 cm, located on the trunk (excluding anogenital skin), neck, or extremities (excluding hands and feet), only when surgical methods are medically less appropriate and patient follow-up can be reasonably assured. 

An important immune function to evaluate in the context of immuno-deficiency, and one that represents a form of nonspecific immunity/host resistance, is the function of natural killer (NK) cells. NK cells are lymphocytes distinct from either B-cells or T-cells, which contribute to immunocompetence by mediating major histocompatibility complex-independent cytotoxicity (Lotzova 1993). For the purposes of these studies, a combined measurement of both basal and augmented NK cell function was used. In this assay, murine splenoc5des were exposed for 24 hours to various concentrations of drugs in the presence or absence of an optimum concentration of recombinant IL-2 (Thomas et al. 1993). The cells were then washed and cocultured for 4 hours with radiolabeled YAC-1 tumor cells (a murine NK-sensitive cell line). Tumor cell lysis was quantitated as described above for the CTL procedure. 

Injection of immunocompetent or nude mice with P8I5 mastocytoma cells transfected with the gene of the CC chemokine MCP-3/CCL7 resulted in peri-tumoral accumulation of DCs and intratumoral recruitment of neutrophils [66]. The expression of CCRl and CCR3 (MCP-3 receptors) on neutrophils may be upregulated by IFN-y induced in T and/or NK cells so that they can directly respond to MCP-3 [70] or, alternatively, recruited by secondary dovmstream mediators. Removal of neutrophils caused an evident delay of MCP-3-elicited tumor rejection, suggesting their cooperative role in tumor inhibition. 

Divinyl ether-maleic anhydride [DIVEMA] is a water-soluble polymer that has antitumor activity against various types of tumors. The biological activities of DIVEMA are due to its ability to activate immunocompetent macrophages and natural killer cells. DIVEMA may be used as a drug carrier for superoxide... 

Ascorbate and Immunocompetence. It is generally accepted that the immune system plays some part in host resistance to cancer, both in the prophylactic sense of an efficient immunosurveillance system destroying neoplastic cells at an early stage in their careers and in the protective sense of retarding the growth of established tumors. Patients maintained on long-term immunosuppressive regimens have an increased incidence of certain forms of cancer, and cancer patients tend to have decreased immunocompetence as measured by standard tests (271). Any practical measure that could enhance immunocompetence could only be beneficial to the cancer patient. 

In cell-mediated immunity, immunocompetence is exercised overwhelmingly by the lymphocytes. In tumors, the degree of stromal lymphocyte infiltration is a measure of the efficiency of host resistance to the neoplastic process. Thus, the degree of lymphocytic infiltration is now accepted as a reliable prognostic indicator. 

A number of studies have analyzed the efficacy of berberine in vivo against transplanted hematologic tumor cell fines as well as during virus-induced leukemia. Specifically, it has been showed that berberine has antitumoral potential in vivo against transplanted mouse acute lymphocytic leukemia P388 [112] and acute myeloid leukemia WEHI-3 [151]. fii addition, this alkaloid was able to inhibit the progression of erythroleukemia induced by mouse rebovirus. Friend, in immunocompetent mice [152]. 

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