Immune checkpoint

Checkpoints immune or immune checkpoints ( IC ) are receptors on the membrane of T-lymphocytes , which their immune response attenuate ( antiinflammatory boost IC) or ( proinflammatory IC) can. So they modulate the immune reaction, for example to protect the body's own cells from attack by the immune system.

The receptors include suitable ligands that are presented or released by other cells. In many tumors , these proteins are upregulated in the course of immune evasion, and the tumor cells are tolerated by the immune system. Immune checkpoint inhibitors are substances that bind permanently to the checkpoints, inhibit them and thus strengthen the immune response. They are used in the course of cancer immunotherapy against anti-inflammatory immune checkpoints to treat tumors, whereby the immune reaction against the tumor is strengthened.

Anti-inflammatory (anti-inflammatory) immune checkpoints

The anti-inflammatory immune checkpoints include the A2AR , B7-H3 (CD276), B7-H4 (synonym VTCN1), BTLA , CTLA-4 , IDO , KIR , LAG3 , PD-1 , TIM-3 and VISTA (V-domain Ig suppressor of T cell activation).

Proinflammatory (inflammation-increasing) immune checkpoints

Five representatives of proinflammatory immune checkpoints come from the TNF receptor superfamily ( CD27 , CD40 , OX40 , GITR and CD137 ), while two belong to the B7-CD28 superfamily ( CD28 and ICOS ).

literature

P. Sharma, JP Allison: Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. In: Cell. Volume 161, number 2, April 2015, pp. 205-214, doi: 10.1016 / j.cell.2015.03.030 , PMID 25860605 .
A. Śledzińska, L. Menger, K. Bergerhoff, KS Peggs, SA Quezada: Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy. In: Molecular oncology. [electronic publication before printing] October 2015, doi: 10.1016 / j.molonc.2015.10.008 , PMID 26578451 .
E. Marcq, P. Pauwels, JP van Meerbeeck, EL Smits: Targeting immune checkpoints: New opportunity for mesothelioma treatment? In: Cancer treatment reviews. Volume 41, number 10, December 2015, pp. 914-924, doi: 10.1016 / j.ctrv.2015.09.006 , PMID 26433514 .

Individual evidence

^ RD Leone, YC Lo, JD Powell: A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy . In: Comput Struct Biotechnol J . 13, April 8, 2015, p. 265–. PMID 25941561 .
↑ AI Chapoval, J Ni, JS Lau, RA Wilcox, DB Flies, D Liu, H Dong, GL Sica, G Zhu, K Tamada, L Chen: B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production . In: Nat Immunol. . 2, No. 3, March 1, 2001, pp. 269-74. PMID 11224528 .
↑ J Leitner, C Klauser, WF Pickl, J Stöckl, O Majdic, AF Bardet, DP Kreil, C Dong, T Yamazaki, G Zlabinger, K Pfistershammer, P Steinberger: B7-H3 is a potent inhibitor of human T-cell activation : No evidence for B7-H3 and TREML2 interaction . In: Eur J Immunol. . 39, No. 7, July 1, 2009, pp. 1754-64. PMID 19544488 .
↑ L Derré, JP Rivals, C Jandus, S Pastor, D Rimoldi, P Romero, O Michielin, D Olive, DE Speiser: BTLA mediates inhibition of human tumor-specific CD8 + T cells that can be partially reversed by vaccination . In: J Clin Invest. . 120, No. 1, January 1, 2010, pp. 157-67. PMID 20038811 .
↑ P Kolar, K Knieke, JK Hegel, D Quandt, GR Burmester, H Hoff, Brunner-Weinzierl MC : CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice . In: Arthritis Rheum. . 60, No. 1, January 1, 2009, pp. 123-32. PMID 19116935 .
↑ GC Prendergast, C Smith, S Thomas, Mandik-Nayak L, Laury-Kleintop L, R Metz, AJ Muller: Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer . In: Cancer Immunol Immunother. . 63, No. 7, July 1, 2014, pp. 721-35. PMID 24711084 .
↑ CT Huang, CJ Workman, D Flies, X Pan, AL Marson, G Zhou, EL Hipkiss, S Ravi, J Kowalski, HI Levitsky, JD Powell, DM Pardoll, CG Drake, DA Vignali: Role of LAG-3 in regulatory T cells . In: Immunity. . 21, No. 4, October 1, 2004, pp: 503-13. PMID 15485628 .
^ GK Philips, M Atkins: Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies . In: Int Immunol. . 27, No. 1, January 1, 2015, pp. 39–46. PMID 25323844 .
↑ WD Hastings, DE Anderson, N Kassam, K Koguchi, EA Greenfield, SC Kent, XX Zheng, TB Strom, DA Hafler, VK Kuchroo: TIM-3 is expressed on activated human CD4 + T cells and regulates Th1 and Th17 cytokines . In: Eur J Immunol. . 39, No. 9, September 1, 2009, pp. 2492-501. PMID 19676072 .
^ L Wang, R Rubinstein, JL Lines, A Wasiuk, C Ahonen, Y Guo, LF Lu, D Gondek, Y Wang, RA Fava, A Fiser, S Almo, RJ Noelle: VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses . In: J Exp Med. . 208, No. 3, March 14, 2011, pp. 577-92. PMID 21383057 .
^ J Hendriks, LA Gravestein, K Tesselaar, RA van Lier, TN Schumacher, J Borst: CD27 is required for generation and long-term maintenance of T cell immunity . In: Nat Immunol. . 171, No. 5, November 1, 2000, pp. 433-40. PMID 11062504 .
^ B O'Sullivan, R Thomas: CD40 and dendritic cell function . In: Crit Rev Immunol. . 23, No. 1, January 1, 2003, pp. 83-107. PMID 12906261 .
^ M Croft, T So, W Duan, P Soroosh: The significance of OX40 and OX40L to T-cell biology and immune disease . In: Immunol Rev. . 229, No. 1, May 1, 2009, pp. 173-191. PMID 19426222 .
^ S Ronchetti, O Zollo, S Bruscoli, M Agostini, R Bianchini, G Nocentini, E Ayroldi, C Riccardi: GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations. . In: Eur J Immunol. . 34, No. 3, March 1, 2004, pp. 613-22. PMID 14991590 .
↑ RS Mittler, J Foell, M McCausland, S Strahotin, L Niu, A Bapat, LB Hewes: Anti-CD137 antibodies in the treatment of autoimmune disease and cancer . In: Immunol Res . 29, No. 1, June 1, 2004, pp. 197-208. PMID 15181282 .
^ D Eastwood, L Findlay, S Poole, C Bird, M Wadhwa, M Moore, C Burns, R Thorpe, R Stebbings: Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4 + effector memory T-cells . In: Br J Pharmacol. . 161, No. 3, October 1, 2010, pp. 512-526. PMID 20880392 .
^ Y Burmeister, T Lischke, AC Dahler, HW Mages, KP Lam, AJ Coyle, RA Kroczek, A Hutloff: ICOS controls the pool size of effector-memory and regulatory T cells . In: J Immunol. . 180, No. 2, Jan 15, 2008, pp. 774-782. PMID 18178815 .

[1] RD Leone, YC Lo, JD Powell: A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy . In: Comput Struct Biotechnol J . 13, April 8, 2015, p. 265–. PMID 25941561 .

[2] AI Chapoval, J Ni, JS Lau, RA Wilcox, DB Flies, D Liu, H Dong, GL Sica, G Zhu, K Tamada, L Chen: B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production . In: Nat Immunol. . 2, No. 3, March 1, 2001, pp. 269-74. PMID 11224528 .

[3] J Leitner, C Klauser, WF Pickl, J Stöckl, O Majdic, AF Bardet, DP Kreil, C Dong, T Yamazaki, G Zlabinger, K Pfistershammer, P Steinberger: B7-H3 is a potent inhibitor of human T-cell activation : No evidence for B7-H3 and TREML2 interaction . In: Eur J Immunol. . 39, No. 7, July 1, 2009, pp. 1754-64. PMID 19544488 .

[4] L Derré, JP Rivals, C Jandus, S Pastor, D Rimoldi, P Romero, O Michielin, D Olive, DE Speiser: BTLA mediates inhibition of human tumor-specific CD8 + T cells that can be partially reversed by vaccination . In: J Clin Invest. . 120, No. 1, January 1, 2010, pp. 157-67. PMID 20038811 .

[5] P Kolar, K Knieke, JK Hegel, D Quandt, GR Burmester, H Hoff, Brunner-Weinzierl MC : CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice . In: Arthritis Rheum. . 60, No. 1, January 1, 2009, pp. 123-32. PMID 19116935 .

[6] GC Prendergast, C Smith, S Thomas, Mandik-Nayak L, Laury-Kleintop L, R Metz, AJ Muller: Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer . In: Cancer Immunol Immunother. . 63, No. 7, July 1, 2014, pp. 721-35. PMID 24711084 .

[7] CT Huang, CJ Workman, D Flies, X Pan, AL Marson, G Zhou, EL Hipkiss, S Ravi, J Kowalski, HI Levitsky, JD Powell, DM Pardoll, CG Drake, DA Vignali: Role of LAG-3 in regulatory T cells . In: Immunity. . 21, No. 4, October 1, 2004, pp: 503-13. PMID 15485628 .

[8] GK Philips, M Atkins: Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies . In: Int Immunol. . 27, No. 1, January 1, 2015, pp. 39–46. PMID 25323844 .

[9] WD Hastings, DE Anderson, N Kassam, K Koguchi, EA Greenfield, SC Kent, XX Zheng, TB Strom, DA Hafler, VK Kuchroo: TIM-3 is expressed on activated human CD4 + T cells and regulates Th1 and Th17 cytokines . In: Eur J Immunol. . 39, No. 9, September 1, 2009, pp. 2492-501. PMID 19676072 .

[10] L Wang, R Rubinstein, JL Lines, A Wasiuk, C Ahonen, Y Guo, LF Lu, D Gondek, Y Wang, RA Fava, A Fiser, S Almo, RJ Noelle: VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses . In: J Exp Med. . 208, No. 3, March 14, 2011, pp. 577-92. PMID 21383057 .

[11] J Hendriks, LA Gravestein, K Tesselaar, RA van Lier, TN Schumacher, J Borst: CD27 is required for generation and long-term maintenance of T cell immunity . In: Nat Immunol. . 171, No. 5, November 1, 2000, pp. 433-40. PMID 11062504 .

[12] B O'Sullivan, R Thomas: CD40 and dendritic cell function . In: Crit Rev Immunol. . 23, No. 1, January 1, 2003, pp. 83-107. PMID 12906261 .

[13] M Croft, T So, W Duan, P Soroosh: The significance of OX40 and OX40L to T-cell biology and immune disease . In: Immunol Rev. . 229, No. 1, May 1, 2009, pp. 173-191. PMID 19426222 .

[14] S Ronchetti, O Zollo, S Bruscoli, M Agostini, R Bianchini, G Nocentini, E Ayroldi, C Riccardi: GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations. . In: Eur J Immunol. . 34, No. 3, March 1, 2004, pp. 613-22. PMID 14991590 .

[15] RS Mittler, J Foell, M McCausland, S Strahotin, L Niu, A Bapat, LB Hewes: Anti-CD137 antibodies in the treatment of autoimmune disease and cancer . In: Immunol Res . 29, No. 1, June 1, 2004, pp. 197-208. PMID 15181282 .

[16] D Eastwood, L Findlay, S Poole, C Bird, M Wadhwa, M Moore, C Burns, R Thorpe, R Stebbings: Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4 + effector memory T-cells . In: Br J Pharmacol. . 161, No. 3, October 1, 2010, pp. 512-526. PMID 20880392 .

[17] Y Burmeister, T Lischke, AC Dahler, HW Mages, KP Lam, AJ Coyle, RA Kroczek, A Hutloff: ICOS controls the pool size of effector-memory and regulatory T cells . In: J Immunol. . 180, No. 2, Jan 15, 2008, pp. 774-782. PMID 18178815 .