Neutralising reactive nitrogen species to make immunotherapy more effective.

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Researchers at the University of Notre Dame discovered that amino acid nitration can inhibit the activation of T cells employed in immunotherapy against cancer and that suppression of reactive nitrogen species (RNS) responsible for nitration can significantly boost the effectiveness of immunotherapy [1].

Abstract

Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to reduced interleukin 2 (IL2) production and proliferation.

A new study suggests that NAD+, which declines with age, may be increased via the de novo pathway.

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Research has discovered that inside every cell in the human body is a kill code designed to trigger self-destruction if it senses a cell is turning cancerous. Across two studies the scientists homed in on the code underlying this mechanism and believe it may lead to a new kind of cancer treatment.

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I have always said the trick with being diagnosed with cancer is living long enough to see newer and better therapies coming out to help you outlive your own diagnosis:

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Scientists at Northwestern University have discovered a “kill code” in every cell of the body that’s triggered by chemotherapy and that causes cancerous cells to self-destruct. What’s more, they’ve learned enough about the code that they’ve figured out how to trigger it without chemo—a finding that they believe could lead to new therapies.

The discovery, reported in the journals Nature Communications and eLife, is a code that’s found in both large and small ribonucleic acids (RNAs). The researchers also have early evidence that the small RNAs, called microRNAs, can be introduced into cells to trigger the kill switch.

“My goal was not to come up with a new artificial toxic substance,” said lead author Marcus Peter, Ph.D., a professor of cancer metabolism at Northwestern’s Feinberg School of Medicine, in a statement. “I wanted to follow nature’s lead. I want to utilize a mechanism that nature developed.”