At the Bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy Journal Article
| Authors: | Intlekofer, A. M.; Thompson, C. B. |
| Article Title: | At the Bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy |
| Abstract: | Tumors can avoid immune surveillance by stimulating immune inhibitory receptors that function to turn off established immune responses. By blocking the ability of tumors to stimulate inhibitory receptors on T cells, sustained, anti-tumor immune responses can be generated in animals. Thus, therapeutic blockade of immune inhibitory checkpoints provides a potential method to boost anti-tumor immunity. The CTLA-4 and PD-1Rs represent two T cell-inhibitory receptors with independent mechanisms of action. Preclinical investigations revealed that CTLA-4 enforces an activation threshold and attenuates proliferation of tumor-specific T lymphocytes. In contrast, PD-1 functions primarily as a stop signal that limits T cell effector function within a tumor. The unique mechanisms and sites of action of CTLA-4 and PD-1 suggest that although blockade of either has the potential to promote anti-tumor immune responses, combined blockade of both might offer even more potent anti-tumor activity. See related review At the Bedside: CTLA-4 and PD-1 blocking antibodies in cancer immunotherapy. © Society for Leukocyte Biology. |
| Keywords: | unclassified drug; nonhuman; antigen expression; lymphocyte proliferation; cytotoxic t lymphocyte antigen 4 antibody; ipilimumab; cancer immunotherapy; protein interaction; antineoplastic activity; t lymphocyte receptor; regulatory t lymphocyte; immune response; cellular distribution; effector cell; chemical structure; immunomodulating agent; receptor; tumor; cytotoxic t lymphocyte antigen 4; tumor vaccine; ligand binding; cd28 antigen; intracellular signaling; programmed death 1 receptor; costimulation; pd-l1; antigen function; costimulatory; inhibitory; coinhibitory; programmed death 1 receptor blocking agent |
| Journal Title: | Journal of Leukocyte Biology |
| Volume: | 94 |
| Issue: | 1 |
| ISSN: | 0741-5400 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2013-07-01 |
| Start Page: | 25 |
| End Page: | 39 |
| Language: | English |
| DOI: | 10.1189/jlb.1212621 |
| PROVIDER: | scopus |
| PMCID: | PMC3685017 |
| PUBMED: | 23625198 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 1 August 2013" - "CODEN: JLBIE" - "Source: Scopus" |
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