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Brakes on the immune system that stop T cells attacking healthy tissue. Tumours pull these brakes to protect themselves; checkpoint inhibitor drugs release them so T cells can attack the cancer.
PD-1 on a T cell, when it meets PD-L1 on another cell, tells the T cell to stand down; CTLA-4 acts earlier, when T cells are first activated. Tumours coat themselves in PD-L1 and exploit this, and antibodies that block PD-1 (pembrolizumab, nivolumab), PD-L1 (atezolizumab, durvalumab) or CTLA-4 (ipilimumab) restore the attack, producing durable remissions in melanoma, lung, kidney, bladder and many other cancers since 2011. The price is autoimmune side effects when the brakes come off everywhere, and only a minority of patients respond, which drives the search for newer checkpoints (LAG-3, TIGIT) and combinations. The 'checkpoint' in 'cell-cycle checkpoint' is an unrelated concept.
In plain words · PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
Showing the target this term concerns: PD-1.
Patients with limited-stage small-cell lung cancer who complete chemoradiotherapy without progression should now be offered up to two years of durvalumab consolidation, which extends life by almost two years on average. This is the first survival improvement for limited-stage disease since twice-daily radiotherapy and prophylactic cranial irradiation, and small-cell lung cancer is no longer a disease where immunotherapy gives only marginal gains.
Perioperative immunotherapy is now standard for resectable lung cancer without a targetable driver. The updated overall survival hazard ratio of 0.89, with a confidence interval crossing one, is the honest state of the evidence on whether it cures more people.
The strongest signal that neoadjuvant immunotherapy makes stage III lung cancer operable as well as more often curable. Twenty-four percentage points more patients reaching surgery is a result that only a neoadjuvant design can produce.
The current standard for unresectable stage III lung cancer, and the clearest evidence in the disease that consolidation immunotherapy converts responses into cures for some patients rather than merely delaying relapse.
Adjuvant immunotherapy entered lung cancer here, and with it the question that still divides practice: whether it is better given before the operation, after it, or on both sides.
For the minority of patients whose tumours express a lot of PD-L1, a single antibody outperforms chemotherapy and is far easier to take. The word minority is the point: the same drug in the same disease at lower PD-L1 gives much less.
Immunotherapy is now part of first-line treatment for extensive-stage small-cell lung cancer everywhere, on the strength of a gain measured in weeks. The size of that gain is the reason small-cell lung cancer remains the clearest unmet need in thoracic oncology.
This is the standard overview of checkpoint immunotherapy for clinicians and scientists, tying together the trial results and the biology of response and resistance that guide today's combination trials.
Shares Checkpoint (two meanings), Immune-related adverse events (irAEs), Hot vs cold tumours, PD-L1-high non-small-cell lung cancer without a driver mutation.
Shares CheckMate 057, CheckMate 017, KEYNOTE-010, CheckMate 9LA.
Shares TIGIT, Hallmark: avoiding immune destruction, LAG-3, Immune-related adverse events (irAEs).
Shares Schreiber, Old and Smyth 2011: cancer immunoediting, Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Hallmark: avoiding immune destruction, Hot vs cold tumours.
Shares CheckMate 057, OAK, CheckMate 017, KEYNOTE-010.
Shares Tumeh 2014: PD-1 blockade works by releasing T cells already present at the tumour edge, Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-L1.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, TIGIT, LAG-3, Checkpoint (two meanings).
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Immune system, Hot vs cold tumours, PD-L1.