Combination cancer immunotherapy and new immunomodulatory targets
- PMID: 26228759
- DOI: 10.1038/nrd4591
Combination cancer immunotherapy and new immunomodulatory targets
Abstract
Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response.
Similar articles
-
Checkpoint inhibitors in bladder and renal cancers: results and perspectives.Immunotherapy. 2015;7(12):1259-71. doi: 10.2217/imt.15.91. Epub 2015 Nov 23. Immunotherapy. 2015. PMID: 26595284 Review.
-
Defining Effective Combinations of Immune Checkpoint Blockade and Oncolytic Virotherapy.Clin Cancer Res. 2015 Dec 15;21(24):5543-51. doi: 10.1158/1078-0432.CCR-14-2009. Epub 2015 Jul 17. Clin Cancer Res. 2015. PMID: 26187615 Free PMC article.
-
The Era of Checkpoint Blockade in Lung Cancer: Taking the Brakes Off the Immune System.Ann Am Thorac Soc. 2017 Aug;14(8):1248-1260. doi: 10.1513/AnnalsATS.201702-152FR. Ann Am Thorac Soc. 2017. PMID: 28613923 Review.
-
Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies.Int Immunol. 2015 Jan;27(1):39-46. doi: 10.1093/intimm/dxu095. Epub 2014 Oct 16. Int Immunol. 2015. PMID: 25323844 Review.
-
Immune checkpoint inhibitor combinations in solid tumors: opportunities and challenges.Immunotherapy. 2016 Jun;8(7):821-37. doi: 10.2217/imt-2016-0002. Immunotherapy. 2016. PMID: 27349981 Free PMC article. Review.
Cited by
-
IL-1 receptor-associated kinase 3 (IRAK3) in lung adenocarcinoma predicts prognosis and immunotherapy resistance: involvement of multiple inflammation-related pathways.Transl Lung Cancer Res. 2024 Sep 30;13(9):2139-2161. doi: 10.21037/tlcr-24-391. Epub 2024 Sep 12. Transl Lung Cancer Res. 2024. PMID: 39430338 Free PMC article.
-
Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses.Oncoimmunology. 2024 Sep 25;13(1):2407532. doi: 10.1080/2162402X.2024.2407532. eCollection 2024. Oncoimmunology. 2024. PMID: 39351443 Free PMC article.
-
Discovery of GNE-6893, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of HPK1.ACS Med Chem Lett. 2024 Sep 3;15(9):1606-1614. doi: 10.1021/acsmedchemlett.4c00319. eCollection 2024 Sep 12. ACS Med Chem Lett. 2024. PMID: 39291002
-
Emerging and Biological Concepts in Pediatric High-Grade Gliomas.Cells. 2024 Sep 5;13(17):1492. doi: 10.3390/cells13171492. Cells. 2024. PMID: 39273062 Free PMC article. Review.
-
Turning to immunosuppressive tumors: Deciphering the immunosenescence-related microenvironment and prognostic characteristics in pancreatic cancer, in which GLUT1 contributes to gemcitabine resistance.Heliyon. 2024 Aug 22;10(17):e36684. doi: 10.1016/j.heliyon.2024.e36684. eCollection 2024 Sep 15. Heliyon. 2024. PMID: 39263146 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials