Talk:Programmed cell death protein 1

Where did the name come from?
Let me point out that this article says absolutely nothing about what this gene/protein has to do with programmed cell death. That seems like the first thing one would want to know. Regards, Looie496 (talk) 14:56, 24 October 2012 (UTC)


 * Agreed. Apparently what PD-1 does is promote programmed cell death in activated T cells which suppresses the immune system thereby promoting self-tolerance. This has now been added to the lead along with appropriate sources to support this function and mechanism. Boghog (talk) 10:43, 7 December 2014 (UTC)

In response to Looie496: The article does explain the connection between the receptor protein PD-1 and programmed cell death in the second paragraph: "The inhibitory effect of PD-1 is accomplished through a dual mechanism of promoting apoptosis (programmed cell death) in antigen specific T-cells in lymph nodes ...." To translate: A receptor sitting on the surface of the T-cells of the immune system, PD-1 can trigger the programmed cell death of its own host cell. PD-1 does this by turning on intracellular enzymes that destroy the cell from within. This mechanism is implied by the terms "apoptosis" and "programmed cell death," but the reader must come to the article with prior knowledge of the mechanism involved, in order to understand the explanation. However, many of the terms relevant to this explanation are explained within Wikipedia, as the numerous hyperlinks indicate.

Also, I question the "low importance" rating of this article. This morning an article in the NYT discussed former President Jimmy Carter's treatment for malignant melanoma. Carter will undergo anticancer immunotherapy that acts at the PD-1 receptor. Malignant melanoma may well become increasingly common in the future, as a result of numerous sun worshipers and UV tanning booth users; this mechanism of anti-cancer treatment may become increasingly important over time. I would think that an article describing a receptor that can play a major role in the treatment of such deadly cancer, one that has afflicted a former president, rates more than low importance. - Aremkay (talk) 15:22, 21 August 2015 (UTC)

Cancer section could become new PD-1 inhibitor or part of immune checkpoint blockade
and be merged with that section of cancer immunotherapy ? - Rod57 (talk) 11:57, 1 August 2015 (UTC)

I think PD-1 inhibitors do merit a specific article to cover them. Cancer immunotherapy is a comprehensive topic already and I think there is enough content to cover to justify a whole article on the PD-1 class. There are 2 approved PD-1 agents, Nivolumab & Pembrolizumab, which each have a fair amount of information on their own pages. Plus a 3rd, Pidilizumab, is in multiple phase 2 trials and is advanced enough to get a name instead of just a code. Timetraveler3.14 (talk) 18:33, 22 August 2015 (UTC)

There is no need to discuss this - keep the Cancer section in abbreviated form and add links to appropriate detailed articles. Be bold Be_bold   Codwiki (talk) 21:58, 6 December 2015 (UTC)

There has been significant breakthroughs with immunotherapy in the past two years in particular and I would like to expand and update the entry of PD-1 given its importance in checkpoint inhibitions treatments. I have assembling a brief bibliography of important reviews and highly cited articles that will serve as the basis for my edits as I provide more information to the sections on PD-1 ligands, general function, and critical importance in cancer treatment and autoimmune therapy. I will continue to collect sources, but here is a brief list of what I will include in the revisions with links:

Chen, Daniel S., and Mellman, Ira. (2013) Oncology meets immunology: the cancer immunity cycle. Cell Immunity. 39. https://www.ncbi.nlm.nih.gov/pubmed/23890059

Curran, Michael A., Montalvo, Welby, Yagita, Hideo, and Allison, James P. (2010) PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. PNAS. Vol. 107 No. 9, 4275-4280. https://www.ncbi.nlm.nih.gov/pubmed/20160101

Herbst, Roy S., Soria, Jean-Charles, Kowanetz, Marcin, Fine, Greg D. (2014) Predictive correlates of response to anti-PD-L1 in cancer patients. Nature. Vol. 0, 1-6. http://www.nature.com/nature/journal/v515/n7528/full/nature14011.html

Restifio, Nicholas P. (2013) A “big data” view of the tumor “immunome.” Cell Immunity. 39. http://www.cell.com/immunity/abstract/S1074-7613(13)00436-6

Topalian, Suzanne, Sharpe, Arlene H. (2014). Balance and imbalance in the immune system: life on the edge. Cell Immunity. 41. http://www.cell.com/immunity/abstract/S1074-7613(14)00400-2

Topalian, Suzanne L., Taube, Janis M., Anders, Robert A., Pardoll, Drew M. (2016). Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nature. Vol. 16, 275-287. https://www.ncbi.nlm.nih.gov/pubmed/27079802

Wang, Jun, Yuan, Ruirong, Song, Wenru, Sun, Jingwei, Liu, Delong, Li, Zihai. (2017) PD-1, PD-L1 (B7-H1) and tumor site immune modulation therapy: the historical perspective. J. Hema. and Onco. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-017-0403-5

Zaretsky, Jesse M., Garcia-Diaz, Angel, Shin, Daniel S., Escuin-Ordinas, Helena, Hugo, Willy, Hu-Lieskovan, Siwen. (2016) Mutations associated with acquired resistance to PD-1 blockade in melanoma]. New England Journal of Medicine. Vol. 375, No. 9, 819-829.http://www.nejm.org/doi/full/10.1056/NEJMoa1604958

I will continue add new sources over the week as I continue research. I also want to strongly agree Aremkay's comment 2015 that I believe that the PD-1 entry should be rated much higher than a low importance article. Anti-PD-1 along with CTLA-4 treatments have been repeatedly shown in recent papers to be very potent anti-cancer therapies that have both been critical in breakthroughs in checkpoint inhibition therapy

— Preceding Immcarle44 comment added by Immcarle44 (talk • contribs) 19:14, 6 February 2017 (UTC)

Clear explanation of PD-1
This abstract from J Clin Pathol (open source) explains PD-1 and PD-L1 more clearly than our own introduction does. This could be a good model for rewriting the article's introduction, by making it less technical so the non-specialist reader could understand it.

J Clin Pathol. 2018 Mar;71(3):189-194. doi: 10.1136/jclinpath-2017-204853. PD-L1. Kythreotou A1, Siddique A1, Mauri FA1, Bower M2, Pinato DJ1.

Abstract

Programmed death ligand 1 (PD-L1) is the principal ligand of programmed death 1 (PD-1), a coinhibitory receptor that can be constitutively expressed or induced in myeloid, lymphoid, normal epithelial cells and in cancer. Under physiological conditions, the PD-1/PD-L1 interaction is essential in the development of immune tolerance preventing excessive immune cell activity that can lead to tissue destruction and autoimmunity. PD-L1 expression is an immune evasion mechanism exploited by various malignancies and is generally associated with poorer prognosis. PD-L1 expression is also suggested as a predictive biomarker of response to anti-PD-1/PD-L1 therapies; however, contradictory evidence exists as to its role across histotypes. Over the years, anti-PD-1/PD-L1 agents have gained momentum as novel anticancer therapeutics, by inducing durable tumour regression in numerous malignancies including metastatic lung cancer, melanoma and many others. In this review, we discuss the immunobiology of PD-L1, with a particular focus on its clinical significance in malignancy.

DOI: 10.1136/jclinpath-2017-204853

--Nbauman (talk) 22:05, 4 June 2018 (UTC)


 * This is a good, relatively recent general review article on PD-1. It's better than a lot of the sources we're using now because (1) It's a review article, which is preferred by WP:MEDMOS to reports of specific findings (2) Many of the older articles are wrong. For example, Boussiotis says that PD-1 is not related to apoptosis. (3) I prefer articles in general medical journals like NEJM and Lancet because they tend to emphasize the most important conclusions. I would like to rewrite the introduction following Boussiotis (which I'm still reading).
 * N Engl J Med. 2016 Nov 3;375(18):1767-1778.
 * Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway.
 * Boussiotis VA
 * DOI: 10.1056/NEJMra1514296
 * Free PMC Article
 * url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575761/
 * --Nbauman (talk) 18:16, 7 June 2018 (UTC)
 * Free PMC Article
 * url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575761/
 * --Nbauman (talk) 18:16, 7 June 2018 (UTC)