Immunity system complexity: go and no go (Introduction)

by David Turell , Sunday, July 12, 2020, 19:48 (1377 days ago) @ David Turell
edited by David Turell, Sunday, July 12, 2020, 19:58

The immune system attacks and stops attacks to avoid causing improper trouble to the normal body components:

https://www.sciencenews.org/article/cells-slow-immune-response-derailing-fight-tumors

"MDSCs are a mix of immature cells from the same family as neutrophils and macrophages, which act as general first responders in the immune system. MDSCs caught scientists’ attention decades ago, but it wasn’t until the last several years that their importance in cancer came into focus.

“'Their normal function is to slow things down,” says William Carson III, a surgical oncologist at Ohio State University in Columbus.

"In a 2016 study of people who received checkpoint blockers for advanced melanoma, patients with lower levels of MDSCs in their blood responded better to the immune therapy and lived longer. That made Carson and his colleagues wonder if getting rid of the suppressor cells could create an environment for checkpoint blockers to work better. And they knew a class of drugs that could potentially achieve this: Brd4 inhibitors.

"In tumor cells, the protein Brd4 regulates the activity of various genes — including some that promote MDSCs. So perhaps a Brd4-inhibiting drug would give checkpoint blockers free rein to do their job.

***

"The team got similar results with several different Brd4 inhibitors and in mice with breast, colon or lung tumors. Though preliminary and unpublished, the findings suggest that Brd4 inhibitors “can get rid of these immune suppressor cells that are an additional brake on the immune system, and allow immune stimulating drugs to work better,” says Carson.

"There are other ways to target those suppressor cells. Timothy Wang, a gastroenterologist at Columbia University Irving Medical Center, and his colleagues went after them using an anti-inflammatory peptide called trefoil factor 2, or TFF2. Previously, Wang and colleagues showed that some T cells release TFF2 to tone down inflammatory responses, and that giving mice TFF2 can boost the immune system and slow tumor growth.

***

"However, a drug’s effectiveness in mice has traditionally shown little correlation with its impact in human patients. For example, anti-PD1 and anti-PDL1 therapies only modestly slowed tumor growth in mice — yet today they’re “the cornerstone for immuno-oncology therapy in humans … and well-tolerated,” Peng says. Another case in point: STING agonists. These drugs, which activate a slew of host defense genes, worked like gangbusters in mice yet have floundered thus far in clinical trials.

"More than a thousand other trials are currently testing checkpoint blockers, alone or in combination with additional drugs and some, like one in people targeting advanced non-small cell lung cancer, are showing some promise. Yet the immune system is so sophisticated, with layers upon layers of brakes, that existing approaches may be “just scratching the surface,” says Peng." (my bold)

Comment: I've used the article on cancer therapy to show the degree of immune complexity (note the bold), and our new-found ability to analyze it and tailor it to create therapies. Thank goodness God gave us this big brain that can be used to improve on His designs.