Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity

By S. Topalian, Charles G. Drake, D. Pardoll. Current Opinion in Immunology, 2012

1,310 citations recorded by the source corpus.

Genetic alterations and epigenetic dysregulation in cancer cells create a vast array of neoepitopes potentially recognizable by the immune system. Immune checkpoint blockade has the capacity to enhance and sustain endogenous immunity against non-mutated tumor-associated antigens as well as uniquely mutant antigens, establishing durable tumor control. Recent evidence from preclinical models highlights the pivotal role of the Programmed Death-1 (PD-1) T cell co-receptor and its ligands, B7-H1/PD-L1 and B7-DC/PD-L2, in maintaining an immunosuppressive tumor microenvironment. Encouraging early clinical results using blocking agents against components of the PD-1 pathway have validated its importance as a target for cancer immunotherapy.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/e3b021f200f3edfcb660b82f5936cb002580eb4a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Kristen E. Pauken
2. Daniel S. Chen
3. E. Wherry
4. C. Zappa
5. Xu Dong Zhang
6. M. Hung
7. Lei Jin
8. Shaker A. Mousa

In Oncology

1. Kristen E. Pauken
2. Daniel S. Chen
3. C. Zappa
4. Xu Dong Zhang
5. M. Hung
6. Lei Jin
7. Shaker A. Mousa
8. J. Hsu

Citations in the corpus

• Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy (2022, background): “As we know, cancer immunotherapy can be improved by blocking PD-1/PD-L1 immune checkpoints by binding PD-L1 on cancer cells to PD-1 on T cells resulting in T cells inactivation, and consequently cancer immune invasion.(192,193) A growing body of evidence suggests autophagy may affect cancer cells’ i”
• Regulation of PD-L1: a novel role of pro-survival signalling in cancer. (2016, background): “The functional importance of PD-L1 has been evidenced by autoimmune diseases in mice deficient in PD-L1 [32, 33].”
• Oncology meets immunology: the cancer-immunity cycle. (2013, background): “…being reported for a broad range of human cancers with several different agents (Hamid et al., 2013a; Herbst et al., 2013; Hodi et al., 2010; Topalian et al., 2012b), providing a compelling argument that cancer immunotherapy is active in a range of indications beyond melanoma, a disease…”
• CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients (2013, neutral): “PD-1- and PD-L1–directed antibodies (14).”
• Overcoming T cell exhaustion in infection and cancer (2015, background): “Studies in preclinical models have greatly contributed to our understanding of the PD-1 pathway in the regulation of T cell immunity [3, 37, 96].”
• PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome (2017, background): “Efforts to use monoclonal antibodies (mAbs) to target and block these immunoinhibitory interactions have led to a new era of immunotherapy based agents for cancer therapy (Freeman et al., 2000; Topalian et al., 2012; Ott et al., 2013).”