Abstract
Checkpoint inhibitor-based immunotherapies that target cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1) pathway have achieved impressive success in the treatment of different cancer types. Yet, only a subset of patients derive clinical benefit. It is thus critical to understand the determinants driving response, resistance and adverse effects. In this Review, we discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome. We focus on recently identified molecular and cellular determinants of response. A better understanding of how these variables cooperate to affect tumour-host interactions is needed to optimize the implementation of precision immunotherapy.
Keywords
ImmunotherapyImmune checkpointTumor microenvironmentCancer immunotherapyBiologyComputational biologyImmune systemCytotoxic T cellCancer researchImmunologyGenetics
MeSH Terms
AnimalsB7-H1 AntigenCTLA-4 AntigenHumansImmunologic FactorsImmunotherapyNeoplasmsTumor Microenvironment
Affiliated Institutions
Related Publications
Advances in immunotherapy for hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is a prevalent disease with a progression that is modulated by the immune system. Systemic therapy is used in the advanced stage and until 2017 co...
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
The immune system influences the fate of developing cancers by not only functioning as a tumour promoter that facilitates cellular transformation, promotes tumour growth and scu...
Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients
A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contr...
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Abstract Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentiall...
Cytotoxic CD8+ T cells in cancer and cancer immunotherapy
The functions of, and interactions between, the innate and adaptive immune systems are vital for anticancer immunity. Cytotoxic T cells expressing cell-surface CD8 are the most ...
Publication Info
- Year
- 2019
- Type
- review
- Volume
- 19
- Issue
- 3
- Pages
- 133-150
- Citations
- 2242
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
2242
OpenAlex
62
Influential
Cite This
Jonathan J. Havel,
Diego Chowell,
Timothy A. Chan
(2019).
The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy.
Nature reviews. Cancer
, 19
(3)
, 133-150.
https://doi.org/10.1038/s41568-019-0116-x
Identifiers
- DOI
- 10.1038/s41568-019-0116-x
- PMID
- 30755690
- PMCID
- PMC6705396