Table 1 The ligands for LAG-3, TIM-3, TIGIT and their interactions

LAG-3

MHC-II

B cells, MON-Mø, DCs, some activated T cells

Negatively regulates T cell responses

[24]

FGL-1

FGL-1 protein is primarily secreted from hepatocytes

Inhibiting antitumor immune responses

[28]

α-synuclein

Neurons, heart, muscle, and other tissues

LAG-3 can recognize α-synuclein fibrils and affect its endocytosis and intercellular transmission, contributing to PD

[223]

Gal-3

Tumor cells, macrophages, epithelial cells, fibroblasts, activated T cells

Inhibiting antitumor T cell responses

[27]

Tim-3

LSECtin

Liver, tumor-associated macrophages, and other tumor tissues

Inhibiting antitumor T cell responses

[26]

Gal-9

APC, MDSCs, Naive CD4 T cells, plasma

Gal-9 mainly induces calcium to flow into the intracellular area of Th1 cells and induces apoptosis

[224]

PtdSer

Released from apoptotic cells

PtdSer and TIM-3 binding contributes to the clearance of apoptotic bodies and antigen cross-presentation by Tim-3⁺ DCs

[104]

CEACAM-1

DCs, monocytes, macrophages, and activated T cells

CEACAM-1/TIM-3 complex formation has a crucial role in regulating autoimmunity and antitumor immunity

[102]

HMGB1

Proliferating tissues or estrogen stimulated cancer cells

Blocking activation and suppresses innate immune responses to nucleic acids

[103]

TIGIT

CD155

DCs, T cells, B cells, macrophages

Increasing the IL-10 secretion

[51]

CD113

Liver, testes, lungs, placenta, and kidneys

Inhibition of T cell and NK cell activity

[121]

CD112

Hematopoietic and non-hematopoietic tissues

Inhibiting the activation of T cells and NK cells

[225]

Nectin4

Tumor cells

Inhibiting NK cell activity

[55]

Fap2

Tumor cells

Inhibiting NK cell toxicity and T cell activity

[56]