PLEASE READ THIS FASCINATING LITTLE ESSAY

Linda on a Thames bridge

Her back is toward Windsor castle.

She looks forward toward Eton College, where the battle of Waterloo was won.

As many of you know, I am currently in Borrego Springs, CA.  Borrego Springs is located in the middle of a vast park, the Anza Borrego Desert State Park.  Our state park is the largest in the United States, beating out South Dakota’s Custer State Park by the area of one buffalo wallow.  Custer is famous for bison; we are famous for fossils (including fossil bison).  Most of my social life here in B.S. stems from participation in the ABDSP Paleontology Society.  We are a more-or-less dedicated group of more-or-less enthusiastic amateurs, who help the Park find, retrieve, clean up and repair, classify, and catalog – old bones and such things, which range in age back some 20 million years.    I joined the group ten or so years ago, chiefly because I enjoyed the field work – hiking all over the desert, looking for fossils.    But that was awhile back.  Now I have the energy and strength of a louse, as well as a balance problem that prevents me from clambering around over rough terrain.  I can still work in the lab and, of course, give geology lectures, but – let’s face it, I am a determent in the field.  Phooey!

Why am I telling you this?  Well, the main reason is to have something to do until the evening news comes on and I can have my vodka and grapefruit- juice cocktail.    But, also, I experienced an epiphany yesterday.  I went out with a dozen or so fellow enthusiasts to survey a bleak and seldom-visited place called June Wash.  It didn’t take me long to realize that I was a net loss to the group.  Vastly too much energy was expended in making sure the old man didn’t kill himself.  We found almost nothing.  Who knows: if the group had been looking for fossils instead of making sure I was still alive, maybe we would have found the Park’s first mastodon?  Why should you care?  Because I have officially renounced field work.  Instead, I intend to write more blogs, and cram even more cancer biology down your throats.  That’s why.

Okay, time for Lester Holt*.  Heavy biology ahead tomorrow.

Now is tomorrow, and you are going to be fascinated by the following biological concepts:         

   Immune checkpoint proteins and their inhibitors.

   Cytotoxic T lymphocytes, sometimes known as Killer T cells.

   Tumor-infiltrating myeloid cells.         

(And if you quit reading here, you are a wimp.)

This blog was stimulated by an article – “Compugen Presents New Results Supporting CGEN-15049 as Potential Cancer Immunotherapy Target” - published in an Israeli business journal which reports on a presentation at a cancer conference in Banff, Canada.  I didn’t understand it.  However, mining the internet for several hours brought me this far along the path to understanding:

The natural immune system consists of various cells, including Killer T-cells, the task of which is to patrol the body and destroy (“lyse”) any cell it finds there that doesn’t belong.  These beat cops of the bloodstream do not “lyse” normal cells, because these benign cells are covered with something called a checkpoint protein, whereas nasty invading cells are bare of such defenses.  Maliciously, cancer cells also can sport these proteins, which are called “checkpoints”, for some reason.  A very important checkpoint protein is called PD-L1, poetically termed the Programmed Death Ligand 1.  If you are an innocent little liver cell, for instance, that finds itself without a coating of PD-L1, you are toast: the immune system will devour you.  Cancers have plenty of external markers that identify them as something that ought to be devoured, but they also can produce a plethora of checkpoint proteins that deceive the immune cops and thus allow the cancer cell to avoid death.  Checkpoint inhibitors are designed to reduce the abundance of these checkpoint proteins, thus allowing the cancer cell to be identified, and eaten, by such things as our Killer T Cells.   

 And what of tumor-infiltrating myeloid cells?  Well, the correct answer to that question is, damned if I know.  Myeloid cells are essential to the production of blood, and these tumor-infiltrating things are needed for “angiogenesis”, which refers to the construction of blood vessels throughout the tumor.  Kill the myeloid cells and the tumor dies a horrible death – I guess.  So maybe these checkpoint inhibitors do a number on the myeloid cells, too.

At several places in all these articles I ran on the observation that, although these inhibitor-based therapies help, they are not a cure.   The thrust of research now seems to be, why?  Also, can we fix that?

But to end optimistically:  Here is a quotation from the article I will attempt to send you to:  With genetic sampling of individual cancers, in the future (around 2025) a patient may be able to get custom-crafted combinations of therapies that rapidly and totally eliminates any particular cancer.” As I said in an earlier blog: make it so.



Easy reading: 

http://www.openicon.com/biotech/glossary/checkpoint.html

*  I like Lester, but I wish it were Brian.  Oh, Lord - what a screw-up!