Immune checkpoint blockade: a common denominator approach to cancer therapy

By S. Topalian, Charles G. Drake, D. Pardoll. Cancer Cell, 2015

3,868 citations recorded by the source corpus.

Summary The immune system recognizes and is poised to eliminate cancer, but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. Drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, anti-PD-L1, and others in early development can unleash anti-tumor immunity and mediate durable cancer regressions. The complex biology of immune checkpoint pathways still contains many mysteries, and the full activity spectrum of checkpoint-blocking drugs, used alone or in combination, is currently the subject of intense study.

Subfields: Epidemiology, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/58a1d5b475d807aa059036595d7f8cfa672bec07

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Citations in the corpus

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study (2017, background): “Inhibition of the PD-L1/PD-1 axis with monoclonal antibodies may be one means of restoring immune surveillance and cell-mediated antitumor activity, and studies of anti-PD-L1/PD-1 agents have shown durable antitumor responses in patients with various advanced cancers [7, 16].”
Regulatory mechanisms of PD-1/PD-L1 in cancers (2024, background): “Owing to the heterogeneity of cancers and genetic differences between individuals, the efficacy of targeting the PD-1/PD-L1 pathway alone is unsatisfactory [366].”
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade (2017, neutral): “The aspects of the host immune response and the tumor intrinsic properties that define therapeutic sensitivity to ICB therapy remain to be elucidated (Sharma and Allison, 2015; Topalian et al., 2015).”
Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade (2017, background): “Therapy with immune checkpoint inhibitors has uncovered a subset of tumors that are highly responsive to an endogenous adaptive immune response (1).”
Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells (2016, background): “Indeed, clinical trials have unequivocally shown that the blockade of immune checkpoints unleashes the spontaneous anti-tumor immune responses in such a powerful way that it has created a paradigm shift in cancer therapy ( Sledzi nska et al., 2015; Topalian et al., 2015).”
Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution. (2016, neutral): “Currently, clinical attention is on generating an inflammatory intratumoral environment through among others immune checkpoint blockade therapy (Topalian et al., 2015).”