Role of 4-1BB in immune responses.

4-1BB is an inducible T cell surface receptor which belongs to the tumor necrosis factor receptor superfamily, a group of cysteine-rich cell-surface molecules. Both human and mouse 4-1BB recently received HLDA nomenclature. Naive T cells lack 4-1BB, which is not only induced upon T cell activation, but also remains on activated T cells. The natural ligand for 4-1BB, 4-1BBL is also induced and is found on activated antigen-presenting cells. Cross-linking of the 4-1BB molecule by agonistic antibody transmits a distinct and potent co-stimulatory signal leading to the activation and differentiation of CD4(+) and CD8(+) cells. 4-1BB transmits signals through the TRAF2-NIK pathway and activates NF-kappaB. Signals relayed through 4-1BB inhibit activation-induced cell death and rescue the immune system during the post-CD28 phase. Antibodies to the 4-1BB molecule can increase GVHD, accelerate the rejection of cardiac allograft and skin transplants, and eradicate established tumors. Interference with the 4-1BB-4-1BBL pathway may be of therapeutic use in the treatment of HIV infection. 4-1BB-deficient mice show dysregulated immune responses and mount elevated Ig responses to T-dependent antigens.

Vinay DS ，Kwon BS 《SEMINARS IN IMMUNOLOGY》

Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival.

Cho HR ，Kwon B ，Yagita H ，La S ，Lee EA ，Kim JE ，Akiba H ，Kim J ，Suh JH ，Vinay DS ，Ju SA ，Kim BS ，Mittler RS ，Okumura K ，Kwon BS ... -  《TRANSPLANT INTERNATIONAL》

Role of 4-1BB:4-1BB ligand in cancer immunotherapy.

Cheuk AT ，Mufti GJ ，Guinn BA 《CANCER GENE THERAPY》

Costimulation of CD28- T lymphocytes by 4-1BB ligand.

DeBenedette MA ，Shahinian A ，Mak TW ，Watts TH ... -  《JOURNAL OF IMMUNOLOGY》

Divergent effects of 4-1BB antibodies on antitumor immunity and on tumor-reactive T-cell generation.

Kim JA ，Averbook BJ ，Chambers K ，Rothchild K ，Kjaergaard J ，Papay R ，Shu S ... -  《CANCER RESEARCH》