Scientists at the Helmholtz Zentrum München recently specified the exact mechanisms via through which tumors block natural killer cells, and how this phenomenon could be reversed. Findings were reported in the European Journal of Immunology.

Role OF Natural Killer Cells (NK cells) In Tumor Control

NK cells are an integral component of the immune system, involved in conferring innate immunity against exogenous and any harmful endogenous substances – including tumor cells. Lymphomas (tumors of lymph node) are cancerous neoplasms that originate from B or T cells of the lymphatic system, and B lymphomas are particularly difficult to treat. It has been reported earlier that NK cells could potentially attack the B lymphomas; however their effectiveness in tumor control is apparently limited.

How Tumor Escape Immune System

Prof. Dr. Ralph Mocikat of the Institute of Molecular Immunology (IMI) at Helmholtz Zentrum München along with his research team discovered that when present in the immediate vicinity of a tumor, NK cells exhibit functional impairment. If placed in a normal environment, they could fully function in a few hours. These findings suggest that certain factors, derived from the tumor, are involved in the deactivation of NK cells.

Key Discovery Of An Inflammatory Cytokine

The scientists identified two tumor-specific factors that played a vital role in the impairment of NK cell function. The first was a specific inflammatory cytokine (IL-10), which was indirectly involved in the impairment and inactivation process. The second factor identified was the surface molecules of the tumor cells (NKG2D ligands). The latter bind to NK cells and down-regulate their activity, thus, protecting the tumor against immune responses. As a result, NK cells are not activated and fail to perform their cytotoxic activity.

Despite these inhibitions, NK cells produce the cytokine interferon-gamma (IFN-γ) during early stages of activation. Researchers discovered that this inflammatory cytokine was essential for activating additional immune responses against the tumor.

Prospects – Optimized Immunotherapy

“Our results show that the transfer of NK cells is a possible strategic option to therapeutically treat B cell lymphoma”, highlighted Mocikat. “According to these findings, this approach can be optimized when transferred NK cells are already activated, in vitro, prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ, or of antibodies against IL-10, could further support the immune activity”.