Lymph nodes, hundreds of small structures located throughout the body, play a pivotal role in immunity, including anti-tumor immune responses. White blood cells, also known as lymphocytes, reside in the lymph nodes and can travel around the body through lymph vessels.
A recent publication in Nature Immunology demonstrates that lymph nodes play a crucial role in responsiveness to immune checkpoint inhibitors (ICIs), a promising type of immunotherapy that remains highly dependent on the presence of immune cells in the tumor microenvironment, the cellular environment in which the tumor exists, which can influence how the tumor grows and responds to treatment. .
The study delves into the world of CD8+ T cells, the immune cells that are critical mediators in the fight against cancer. These cells, which reside in the lymph nodes, remain primed and ready to act if the immune system encounters cancer cells.
Like most types of immune cells, CD8+ T cells can become “exhausted” after prolonged stimulation. In terms of the anti-tumor immune response, CD8+ T cell exhaustion can occur when a cell encounters and kills cancer cells. Once an immune cell becomes exhausted, it can no longer kill cancer cells optimally. Before reaching the exhaustion state, CD8+ T cells actively self-renew and drive the proliferation of CD8+ cells required for ICI effectiveness.
The study demonstrates, in a pre-clinical setting, that a subset of CD8+ T cells in the lymph node provides an initial burst of immune activity that could benefit the anti-tumor immune response. Notably, the researchers found that this subset of CD8+ T cells in the lymph node not only provides an immune boost but also facilitates the dissemination of activated CD8+ T cells. Because ICIs require immune components, the movement of CD8+ T cells inside the lymph node is particularly integral in patients receiving ICI treatments.
Overall, the study uncovers a previously unknown role for the lymph nodes in enhancing the immune response following ICI treatment. These findings, though originating from pre-clinical animal and laboratory studies, could potentially revolutionize future drug development and clinical practice.
Sources: Nat Immunol, Immunol