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The blockade of immune checkpoints in cancer immunotherapy
  • D. Pardoll
  • Biology, Medicine
    Nature Reviews Cancer
  • 22 March 2012
Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
STATs in cancer inflammation and immunity: a leading role for STAT3
Signal transducer and activator of transcription proteins are central in determining whether immune responses in the tumour microenvironment promote or inhibit cancer, and STAT3 is a promising target to redirect inflammation for cancer therapy.
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune Escape
Induction of the B7-H1/PD-1 pathway may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity and may explain how melanomas escape immune destruction despite endogenous antitUMor immune responses.
Tumour immunology: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment
Signal transducer and activator of transcription 3 (STAT3) propagates several levels of crosstalk between tumour cells and their immunological microenvironment, leading to tumour-induced immunosuppression and has emerged as a promising target for cancer immunotherapy.
Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity, and tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.
Immune checkpoint blockade: a common denominator approach to cancer therapy.
The immune system recognizes and is poised to eliminate cancer but is held in check by inhibitory receptors and ligands, so drugs interrupting immune checkpoints, such as anti-CTLA-4, anti-PD-1, and others in early development, can unleash anti-tumor immunity and mediate durable cancer regressions.
Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis
It is shown that VEGF expression correlates with Stat3 activity in diverse human cancer cell lines and indicates that Stat3 represents a common molecular target for blocking angiogenesis induced by multiple signaling pathways in human cancers.
Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens.
MHC class I-restricted antigens are efficiently transferred in vivo to bone marrow-derived antigen-presenting cells, which suggests that human leukocyte antigen matching may be less critical in the application of tumor vaccines than previously thought.