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. 2018 Dec 6;9:2894. doi: 10.3389/fimmu.2018.02894

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Copyright © 2018 da Silva, Montero-Montero, Ferreira and Quintanilla.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Functions of HLA-G and Qa-2 on immune cells in the tumor microenvironment. HLA-G, either on the surface of tumor cells or in its soluble form or associated with exosomes, inhibits different traits of immune cells through interaction with the inhibitory receptors ILT2 and ILT4, allowing tumor cells to escape from immune surveillance. Also, HLA-G has been reported to interact with KIR2DL4 receptor to activate NK cells, although this is a matter of controversy (see the text). On the other hand, Qa-2 has been reported to activate NK cells and CD8⁺ CTLs that inhibit tumor cell growth and mediate tumor rejection. Inhibition of NK cells by Qa-2 was also reported in vitro, and Ly49C postulated as a Qa-2 inhibitory receptor, see the text. Receptors on immune cells involved in the response to Qa-2 are presently unknown. Likewise, whether Qa-2 is released to the extracellular milieu associated to exosomes remains to be investigated.