Cancer Discov. 2018 Sep;8(9):1069-1086. doi: 10.1158/2159-8290.CD-18-0367. Epub 2018 Aug 16.
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy.
Immune
checkpoint blockade is able to induce durable responses across multiple
types of cancer, which has enabled the oncology community to begin to
envision potentially curative therapeutic approaches. However, the
remarkable responses to immunotherapies are currently limited to a
minority of patients and indications, highlighting the need for more
effective and novel approaches. Indeed, an extraordinary amount of
preclinical and clinical investigation is exploring the therapeutic
potential of negative and positive costimulatory molecules. Insights
into the underlying biological mechanisms and functions of these
molecules have, however, lagged significantly behind. Such understanding
will be essential for the rational design of next-generation
immunotherapies. Here, we review the current state of our understanding
of T-cell costimulatory mechanisms and checkpoint blockade, primarily of
CTLA4 and PD-1, and highlight conceptual gaps in knowledge.
Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1069-86. ©2018 AACR.
Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1069-86. ©2018 AACR.
- PMID:
- 30115704
- DOI:
- 10.1158/2159-8290.CD-18-0367
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