Concluding Remarks

In this review we describe how NK cells communicate with tumor cells, especially at the tumor microenvironment which turns to have a major role in the modulation of NK functions. There are yet several vital issues to address; solving these questions will reveal some of the fundamentals of NK biology. Among these are: (1) Identification of the tumor-ligands for NK activating receptors, and in particular for the NCRs, to understand the basic recognition of transformed cells. (2) Elucidating NK surveillance of early-transformed cells at different tissues, and its disturbance in progressed tumors. (3) The characterization of trafficking of functional NK-subsets into the tumor site, and these subsets retention or further migration. (4) Development of intravital image techniques to observe NK functions inside tumors in order to understand the killers' activities in the crime scene. (5) Delineate NK relationships with other immune-cells at the tumor area. (6) Gain mechanistic comprehension of the local and the systemic NK suppression by tumors.

New insights can lead to new treatments that will harness the robust NK activity against tumors. Based on understanding how tumor-microenvironment disarms NK cells, we will be able to aim sustained NK activity against the tumor spread.

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