In a mouse model of chronic viral infection, there are very few virus-specific killer T cells in the blood, Emory Vaccine Center scientists report in a new paper in PNAS. This has implications for efforts to enhance cancer immunotherapy, because in both chronic viral infection and cancer, the same types of exhausted T cells accumulate.
CD8 T cells in lymphoid tissue (spleen) – from Im et al Nature (2016)
Vaccine Center director Rafi Ahmed’s lab has learned a great deal about exhausted T cells by studying the LCMV (lymphocytic choriomeningitis virus) model. In this situation, virus-specific CD8 T cells accumulate in lymph nodes and in other organs, without circulating in the blood, because they acquire a residency program, the PNAS authors write. Postdoc Sejin Im’s 2016 paper defined these “stem-like” cells – he is the first author of the new one as well.
A related phenomenon can be seen in the Kissick lab’s recent paper on immune “outposts” in kidney and other urologic tumors. The stem-like cells stay within the tumor and give rise to similar progeny. One consequence may be that treatments aimed at reactivating those cells need to get inside the tumor.
Lymphedema, or swelling because of the impaired flow of lymph fluid, can occur as a consequence of cancer or cancer treatment. Chemotherapy can damage lymph ducts, and often surgeons remove lymph nodes that may be affected by cancer metastasis. Lymphedema can result in painful swelling, impaired mobility and changes in appearance.
Young-sup Yoon, MD, PhD
Emory scientists, led by cardiologist and stem cell biologist Young-sup Yoon, have shown that they can isolate progenitor cells for the lining of lymph ducts. This finding could lead to doctors being able to regenerate and repair lymph ducts using a patientâ€™s own cells.Â The results are described in a paper published recently in the journal Circulation.
The authors used the cell surface marker podoplanin as a handle for isolating the progenitor cells from bone marrow. Previous research has demonstrated that podoplanin is essential for the development of the lymphatic system.
In the paper, the authors use several animal models to show that the progenitor cells could contribute to the formation of new lymph ducts, both by becoming part of the lymph ducts and by stimulating the growth of nearby cells.
â€œThis lymphatic vesselâ€“forming capability can be used for the treatment of lymphedema or chronic unhealed wounds,â€ Yoon says.
Isolated lymphatic endothelial cells (red) incorporate into lymph ducts (green) in a model of wound healing in mice.
The authors also show that mice with tumors show an increase in the number of this type of circulating progenitor cells. This suggests that tumors send out signals that encourage lymph duct growth â€“ a parallel to the well-known ability of tumors to drive growth of blood vessels nearby. Yoon says the presence of these cells could be a marker for tumor growth and metastasis.Â Because tumors often metastasize along lymph ducts and into lymph nodes, studying this type of cells could lead to new targets for blocking tumor metastasis.
A recent review in the journal Genes & Development summarizes additional functions of the lymphatic system in fat metabolism, obesity, inflammation, and the regulation of salt storage in hypertension.