Cancer and Immunology
Natural Killer cells limit aggressiveness of the tumors.
Cancer associated fibroblasts such as Pancreatic Stellate Cells (PSA) and fat cells infiltrating the tumor microenvironment and those surrounding the tumors can cause the tumors to become more aggressive by inhibiting the function of NK cells and promoting survival and expansion of immune suppressive cells such as MDSCs and T regulatory cells. Decreased numbers and function of NK cells will in turn limit their tumor suppressive effect resulting in survival and expansion of cancer stem cells/poorly differentiated tumors since NK cells limit growth and expansion of CSCs/poorly differentiated tumors by both killing of these tumors and differentiation of these tumors. To counter such suppressive tumor microenvironment super-charged NK cells can be delivered to the patients.
Time lapse image of Natural Killer (NK) cells killing oral cancer stem cells (CSCs) which are more aggressive subset of tumor cells (bottom panel) but not the differentiated oral tumors which are much less aggressive type of tumor cells (top panel). Dead tumors appear yellow-orange color in the pictures.
Super-charged NK cells growing in the plate.
Chemotherapeutic drugs only kill aggressive tumors that are differentiated with Natural Killer cells. When tumor differentiation by the NK cells is blocked, then tumors become resistant to chemotherapeutic drugs.
Oral squamous cancer stem cells (OSCSCs) were implanted and grown in the oral cavity of humanized BLT mice for several weeks before the tumors were resected, dissociated and single cells were grown in culture dishes. Larger numbers of cells and faster tumor cell growth were seen from these tumor implanted mice (left panel). When Super-charged Natural Killer cells were injected intravenously in OSCSC tumor bearing mice, tumors did not grow and when single cells were prepared from the small tumors that grew, the tumor cells were unable to grow in cultures since they exhibited differentiated phenotype (middle panel). When tumor differentiation by the NK cells were blocked, tumors grew to large sizes in mice and when they were resected and grown in culture dishes, they grew faster and to a large number (right panel)
Schematic representation of the steps required for super-charging NK cells.
When NK cells in the stage 2 of maturation are cultured with osteoclasts and given sAJ2 probiotic bacteria, NK cells proliferate and expand and acquire their super-charged phenotype in which they become highly aggressive killers and secrete large amounts of IFN-g which are required for the differentiation of tumors. Most cancer patients’ NK cells are in stage 3 since they do not have the ability to kill tumors or differentiate them due to their defective killing and cytokine secretion capabilities.