Good news! Cancer is history (soon)! It is a long step-by-step battle, but humans are winning!
"... In a study of mice, the researchers found that bacteria naturally found in the lungs help to create an environment that suppresses T-cell activation in the lymph nodes near the lungs.
The researchers did not find that kind of immune-suppressive environment in lymph nodes near tumors growing near the skin of mice. ...
For many years, scientists have known that cancer cells can send out immunosuppressive signals, which leads to a phenomenon known as T-cell exhaustion. The goal of cancer immunotherapy is to rejuvenate those T cells so they can begin attacking tumors again.
One type of drug commonly used for immunotherapy involves checkpoint inhibitors, which remove the brakes on exhausted T cells and help reactivate them. This approach has worked well with cancers such as melanoma, but not as well with lung cancer.
... recent work has offered one possible explanation for this: ... that some T cells stop working even before they reach a tumor, because of a failure to become activated early in their development. In a 2021 .. identified populations of dysfunctional T cells that can be distinguished from normal T cells by a pattern of gene expression that prevents them from attacking cancer cells when they enter a tumor. ...
these T cells failed to become fully activated, as a result of inhibition by another population of T cells called regulatory T cells.
These regulatory T cells became strongly activated in lymph nodes that drain from the lungs, but not in lymph nodes near tumors located in the flank, the researchers found. Regulatory T cells are normally responsible for making sure that the immune system doesn’t attack the body’s own cells. However, the researchers found that these T cells also interfere with dendritic cells’ ability to activate killer T cells that target lung tumors. ..."
From the highlights and abstract:
"Highlights
• Lung LN-specific enrichment in IFN-γ induces suppressive Th1-like effector Treg cells
• LN microniches skew Treg cells to be Th1-like and drive DC1 suppression
• Suppressed DC1s prime dysfunctional CD8+ T cell responses against lung cancer
• IFN-γ blockade repolarizes Treg cells and restores CTL priming against lung cancer
Summary
Local environmental factors influence CD8+ T cell priming in lymph nodes (LNs). Here, we sought to understand how factors unique to the tumor-draining mediastinal LN (mLN) impact CD8+ T cell responses toward lung cancer. Type 1 conventional dendritic cells (DC1s) showed a mLN-specific failure to induce robust cytotoxic T cells responses. Using regulatory T (Treg) cell depletion strategies, we found that Treg cells suppressed DC1s in a spatially coordinated manner within tissue-specific microniches within the mLN. Treg cell suppression required MHC II-dependent contact between DC1s and Treg cells. Elevated levels of IFN-γ drove differentiation Treg cells into Th1-like effector Treg cells in the mLN. In patients with cancer, Treg cell Th1 polarization, but not CD8+/Treg cell ratios, correlated with poor responses to checkpoint blockade immunotherapy. Thus, IFN-γ in the mLN skews Treg cells to be Th1-like effector Treg cells, driving their close interaction with DC1s and subsequent suppression of cytotoxic T cell responses."
Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer (no public access)
A new MIT study explains why dendritic cells (green) in lymph nodes that drain from the lungs fail to stimulate killer T cells (white) to attack lung tumors.
Graphical abstract
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