Modulation of monocyte-tumour cell interactions by Mycobacterium vaccae.

Immunotherapy with Mycobacterium vaccae as an adjuvant to chemotherapy has recently been applied to treatment of patients with cancer. One of the mechanisms of antitumour activity of Mycobacterium bovis bacillus Calmette-Guérin (BCG), the prototype immunomodulator, is associated with activation of monocytes/macrophages. These studies were undertaken to determine how M.

Depressed tumor necrosis factor alpha and interleukin-12p40 production by peripheral blood mononuclear cells of gastric cancer patients: association with IL-1R-associated kinase-1 protein expression and disease stage.

Our study investigated the ability of peripheral blood mononuclear cells (PBMCs) isolated from patients with different clinical stages of gastric cancer to produce proinflammatory (tumor necrosis factor alpha [TNFalpha], interleukin 12p40 [IL-12p40] and interleukin 6 [IL-6]) and antiinflammatory (interleukin-10 [IL-10]) cytokines after stimulation with lipopolysaccharide (LPS) or tumor cells, and its correlation with IL-1R-associated kinase-1 (IRAK-1) protein expression. The data showed that TNF production by tumor cell-stimulated PBMCs obtained from patients with advanced gastric cancer was significantly depressed in comparison to the control group. The response to LPS was less affected.

Involvement of pattern recognition receptors in the induction of cytokines and reactive oxygen intermediates production by human monocytes/macrophages stimulated with tumour cells.

Background: Some ligands of pattern recognition receptors (PRR) are present on tumour cells. The role of PRR in signalling for cytokine and reactive oxygen intermediates (ROI) production by monocytes and monocyte-derived macrophages (MDM) stimulated with tumour cells was studied.

Materials And Methods: Monocytes/MDM were pretreated with PRR ligands or anti-PRR monoclonal antibodies (mAbs) and stimulated with tumour cells.

Antitumor response of CD14+/CD16+ monocyte subpopulation.

Objective: Two main subpopulations of human blood monocytes are distinguished on the basis of CD14 and CD16 expression: the major population with enhanced expression of CD14 (CD14++ monocytes) and the minor one with a weak expression of CD14 coexpressing CD16 (CD14+/CD16+ monocytes). As monocytes and macrophages are involved in antitumor response of the host, we assessed the ability of CD14+/CD16+ monocytes to produce cytokines (intracellular expression, release) and reactive oxygen and nitrogen (ROI, RNI) intermediates following stimulation in vitro with tumor cells.

Materials And Methods: Monocytes were isolated by elutriation and their subpopulations by FACS sorting.

Extracellular matrix proteins modulate cytokine production by monocytes during their interactions with cancer cells.

Background: This study examined the role of extracellular matrix compounds (EMC) in the alteration of tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) production by human monocytes stimulated with cancer cells.

Materials And Methods: Monocytes were cultured with cancer cells in the absence or presence of EMC and cytokine release was measured by ELISA. In some experiments monocytes preincubated with monoclonal antibodies (mAbs) against CD29 and CD44 were used.

Tumor cell-induced deactivation of human monocytes.

Although blood monocytes exhibit significant cytotoxic activity against tumor cells, the function of tumor infiltrating macrophages (TIM) is depressed in cancer patients. This study addresses the question of how the antitumor response of human monocytes, assessed by production of cytokines (tumor necrosis factor alpha, TNF; IL-10; IL-12p40) and cytotoxicity, is altered by exposure to cancer cells. Tumor cell--pre-exposed monocytes restimulated with tumor cells showed significantly decreased production of TNF, IL-12, increased IL-10 (mRNA and release) and inhibition of IL-1 receptor-associated kinase-1 (IRAK-1) expression.

Immunophenotypic changes and induction of apoptosis of monocytes and tumour cells during their interactions in vitro.

The in vitro model of tumour infiltrating macrophages (TIM)-tumour interactions in which monocytes and monocyte-derived macrophages (MDM) are cultured with cancer cells was used to assess immunophenotypic changes of interacting cells. Following short cocultures, monocytes, MDM and tumour cells were sorted out by FACS and the expression of several determinants was evaluated. Monocytes showed the induction of CD44v6 and v7/8, and up-regulation of CD16 (Fc gamma RIII), CD54 (ICAM-1), CD68 (macrophage maturation marker) and CD86 (costimulatory molecule B7.