Cancer immune control: another piece of the puzzle.

Tumor microenvironment contains several different cell types, including immune system cells such as T, B, NK and dendritic cells (see https://archive-sciencewhatelse.jimdo.com/immune-system/ ), which affect both cancer development and, in parallel, the response to cancer treatment.

Mechanism of tumor immune control. The mechanism governing the activity of NK cells in the immune control of tumors has been recently described. Cells undergoing malignant transformation increase the expression on the surface of proteins activating NK cells. Activated NK cells produce molecules, called chemokines, required to recruit the Conventional Dendritic Cells subtype 1 (cDC1). In the tumor microenvironment, cDC1 cells recruitment close to NK cells, contributing to immune system activation against cancer cells, is associated with cancer patients’ survival in different tumor types.

Tumor evasion of the immune control. Cancer cells have developed strategies to evade the immune control, for instance, by producing a molecule named PGE that inhibits NK and cDC1 cells at multiple levels. Human cDC1 are normally excluded from the tumor microenvironment and their absence might contribute to cancer progression, thus suggesting that the mechanism described in mice, through which PGE weakens the spontaneous anti-tumor immunity, can likely be similar in humans as well.

Boosting anti-tumor immune response. Therefore, increasing cDC1 presence in tumor microenvironment might be an efficient way to enhance the effects of immune-therapies against tumor. This could be achieved by augmenting chemokines production by NK cells, which would prevent cDC1 recruitment.

In this view, PGE represents an ideal tool, as it dampens cDC1 function both i) indirectly, by downregulating NK cells survival and function (namely the production of the chemokines required to recruit cDC1 cells), and ii) directly, by reducing cDC1 responsiveness to attractants, through the downregulation of receptors normally promoting cDC1 recruitment into tumors.

Reference: NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control. Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, Rogers NC, Sahai E, Zelenay S, Reis E Sousa C. Cell 2018.