Emerging concepts for immune checkpoint blockade-based combination therapies Journal Article
| Authors: | Zappasodi, R.; Merghoub, T.; Wolchok, J. D. |
| Article Title: | Emerging concepts for immune checkpoint blockade-based combination therapies |
| Abstract: | Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from “self,” generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization. Checkpoint blockade has formally demonstrated that reactivating anti-tumor immune responses can regress tumors. However, this only occurs in a fraction of patients. Incorporating these therapies in more powerful combinations is thus a logical next step. Here, we review functional roles of immune checkpoints and molecular determinants of checkpoint-blockade clinical activity. Limited-size T cell-infiltrated tumors, differing substantially from “self,” generally respond to checkpoint blockade. Therefore, we propose that reducing tumor burden and increasing tumor immunogenicity are key factors to improve immunotherapy. Lastly, we outline criteria to select proper immunotherapy combination partners and highlight the importance of activity biomarkers for timely treatment optimization. © 2018 Elsevier Inc. |
| Keywords: | cancer immunotherapy; tumor immunology; immune checkpoint blockade; immunotherapy-based combinations |
| Journal Title: | Cancer Cell |
| Volume: | 33 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2018-04-09 |
| Start Page: | 581 |
| End Page: | 598 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2018.03.005 |
| PROVIDER: | scopus |
| PMCID: | PMC5896787 |
| PUBMED: | 29634946 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 May 2018 -- Source: Scopus |
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