A new article in the Science Immunology journal reveals vital information on how immune checkpoint blockade (ICB) therapy is related to the enhancement of T cell activity by the body against the tumor. The study executed by the MIT scientists highlights that the spleen’s activity is crucial in increasing the populations of T cells that can react with the tumor during the ICB treatment.
Unmasking Immunotherapy
Immunotherapy, which is among the fastest-developing emergent treatment for solid tumors, has been utilized in the past few years to treat cancers, however, how it enhances the anti-tumor immune response has not been clearly articulated. The new study presented here offers such explanations.
The authors performed immunophenotyping of tumor-associated CD8+ T cells in lung cancer mice models in the different anatomical block tissues pre- and post-ICB therapy. They observed that ICB treatment causes an increase of tumor-reactive T cells both high and low affinty for the antibody in the spleen.
The Spleen: An Unanticipated Contributor
There is some fascination in the last few years on T cells that are found in tumors; however, this study brings out a very critical point on the contribution of secondary lymphoid organs like the spleen in the anti-tumor immunity response.
“T cell populations in the spleen increased dramatically after checkpoint blockade treatment, which came as a surprise to us,” said lead author Duncan Morgan. “This indicates that spleens are involved in expanding T cell populations that are in circulation and ready to penetrate into tumors.”
Examining T Cell Subsets More Closely
Again the researchers turned to single-cell RNA sequencing analysis to study how the individual T cell populations are different. They found a number of different populations including progenitor, intermediate and exhausted T-cell phenotypes.
Of significance was the finding that the population of T cells which were “intermediate” with respect to their endocytic receptors manifesting both CXCR3 and CX3CR1 were found in greater numbers in the white pulp of the spleen after ICB treatment compared to before treatment. These were new effector CD4+ T cells with some characteristics of memory and some characteristics of effector cells, which suggests that these cells are likely to produce promises against tumors.
Impact and Future Directions
A better understanding of the sites and mechanisms by which ICB therapy helps T cell responses may help in improving cancer therapy. This study is timely as it leads to new methods of increasing the priming and expansion of T cells in the spleen thus enhancing the effects of immunotherapy.
“The work provides insights into ways in which cancer immunotherapy can be improved,” senior author of the paper, Stefani Spranger, said. “New T cell tropism could complement checkpoint blockade by focusing on the spleen and these intermediate T cell populations.”
Moving Forward
This investigation was done in mouse models, however, the authors provide evidence for the presence of similar T cell population dynamics in patients with cancer as well. More work will be needed to understand the role of the spleen in human anti-tumor immunity and to create cures that capitalize on this mechanism.
The growing understanding of the nature of immunology in cancer is giving way to the emergence of high focused and effective treatment options. This study is a significant step in the complexities of tumor interactions with T cells, T cell tumor immunotherapy in the developing context of the cell.
