Immune Cell Triads Unveil a Critical Role in Fighting Solid Tumors

The Cancer Research Institute (CRI) is excited to share the latest study from CRI Lloyd J. Old STAR Andrea Schietinger, PhD, from Memorial Sloan Kettering Cancer Center, published in Cancer Cell. The study focuses on the interaction between different immune cells to eliminate tumors.   

Dr. Schietinger and her team found that CD4 T cells play a unique role in helping cytotoxic CD8 T cells fight against solid tumors in adoptive T cell therapy (ACT). 

CD4 T cells, commonly known as ’T helper cells,’ have long been acknowledged for their vital role in initiating the activation of CD8 T cells through cytokine secretion and antigen presentation. The activated CD8 T cells alone are established frontline effectors of the immune response aimed at eliminating tumor cells in ACT.

However, Dr. Schietinger and her team’s latest research challenges this conventional wisdom.

Their new discovery has revealed an uncharted aspect of CD4 T cells’ function: their direct involvement in the effector phase of CD8 T cells, thereby aiding in tumor eradication. This process relies on the formation of specialized three-cell complexes known as ’immune triads.’ 

These immune triads contain tumor-specific cytotoxic CD8 T cells, CD4 T cells, and antigen-presenting dendritic cells – all engaged together. Dendritic cells are special immune cells that act like messengers in the body and play a key role in triggering the immune system’s response to fight off infections and diseases. The location of immune triads within the tumor is crucial for effectively combating cancer, outweighing the importance of their quantity within the tumor. 

This is the first time CD4 cells have been shown to be directly involved in the effector phase of anti-tumor immune responses. The study notes CD4 T cells do not directly attack cancer cells in this process. Instead, they help reprogram cytotoxic CD8 T cells through cytokine signals and direct interactions between the two types of T cells in the effector phase. 

These findings are significant for their role in ACT and for their potential application in multiple therapeutic approaches. These strategies can be utilized for treating cancers through diverse approaches such as immune checkpoint blockade (ICB) therapies and cancer vaccines. 

Overall, Dr. Schietinger’s innovative approach sheds new light on the dynamics of immune cell interactions with the tumor microenvironment and their implications for developing effective cancer immunotherapies.