Immunology

The researches find that the Immunotherapy have revolutionized the care of many cancers, therefore teaching the body’s own immune cells to recognize and attack tumor cells. Leading the way are drugs known as checkpoint inhibitors, which block a kind of “white flag” that tumors wave as a peace signal to T cells that would very much like to kill them. Really, this white flag is a protein called PD-L1 many tumors coat themselves in it.

Immunotherapy have revolutionize

When PD-L1 on the surface of a cancer cell sees its partner, PD1, on T cells; these T cells are tricked into letting the cancer cell live. To counteract this dirty trick; checkpoint inhibitor drugs block the functions of PD-L1 on tumor cells (e.g. atezolizumab) or PD1 on T cells (e.g. pembrolizumab), allowing T cells to go about their cancer-killing business.

For reasons that have been largely unknown; some patients respond to checkpoint inhibitor therapies, while others do not. A University of Colorado Cancer Center study published in the journal Cancer Immunology Research offers insight and possibly an inroad into this problem: In mouse models of B-cell lymphoma, adding another drug, called a histone deacetylase (HDAC) inhibitor; sensitized cancers to anti-PD1 therapy.

Models of B-cell lymphoma

“They think this combination is definitely worth trying;” says Jing Wang, MD, Ph.D., investigator at CU Cancer Center and associate professor in the CU School of Medicine Department of Immunology and Microbiology. The reason this combination works is a bit complex. However; it may help to explain not only why some patients fail to respond to anti-PD1 immunotherapy; but also why HDAC inhibitors; which have seemed so promising in the lab, have been largely unsuccessful with patients.

The reason has to do with another set of proteins, called major histo compatibility complex (MHC). In fact, MHC describes a few classes of proteins think of them like silver platters, only in this case; instead of serving food, MHC proteins serve antigens. Basically, MHC proteins grab and little bits of proteins from inside a cell and present them on the cell surface for inspection by our T cells.

Classes of proteins

And when our T cells recognize a dangerous antigen sitting on an MHC platter; they attack that cell (you know, unless the T cell is deactivated by the PD1/PD-L1 interaction). If a cancer cell has no MHC proteins, it doesn’t matter if immunotherapy blocks the PD1/PD-L1 interaction—without MHC; the cancer cell presents no antigens and so the immune system sees no danger. “T cells recognize antigens in the context of MHC. Without MHC, you can’t present an antigen. And about 60 percent of diffuse large B cell lymphomas down regulate MHC,” Wang says.