PD-L2 binds to its receptor PD-1 with
dissociation constant Kd of 11.3 nM.[17] Binding to PD-1 can activate pathways inhibiting
TCR/
BCR-mediated immune cell activation[12] (for a more detailed discussion see
PD-1 signaling). PD-L2 plays an important role in
immune tolerance and
autoimmunity.[18] Both PD-L1 and PD-L2 can inhibit T cell proliferation and inflammatory cytokine production.[17] Blocking PD-L2 has been shown to exacerbate
experimental autoimmune encephalomyelitis.[18] Unlike PD-L1, PD-L2 has been shown activate the immune system. PD-L2 triggers
IL-12 production in murine
dendritic cells leading to T cell activation.[17] Others have shown that treatment with PD-L2
Ig led to
T helper cell proliferation.[18]
The direct role of PD-L2 in cancer progression and
immune-tumor microenvironment regulation is not as well studied as the role of PD-L1.[16] In mouse cell cultures, PD-L2 expression on tumor cells suppressed
cytotoxic T cell-mediated immune responses.[20]
Indirectly, PD-L2 may have utility as a
biomarker or prognostic indicator. PD-L2 expression has been shown to predict response to PD-1 blockade with
pembrolizumab independently of PD-L1 expression.[16] However, PD-L2 does not putatively predict
outcome in cancer, with some studies suggesting it predicts negative
prognoses[21][22][23] and other studies suggesting it predicts positive prognoses.[24]
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^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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