Ludwig Cancer Research investigators have deciphered a complex molecular relationship between cancer and immune cells. Evidencing the vital role of T-cell invasion in tumors that kill cancers, the findings can be used to inform the design of novel cell-based and other immunotherapies for cancer.
Two important chemokines are involved in T-cell infiltration across all solid tumors, CCL5 and CXCL9.
“Their simultaneous presence in tumors is a key requirement for the engraftment of T-cells and the establishment of a T-cell-inflamed tumor” reports Dr. George Coukos, director of the Lausanne Branch of the Ludwig Institute for Cancer Research.
The Swiss team found that CCL5 and CXCL9 are constantly associated with CD8+ T-cell infiltration of solid tumors. The CD8+ T-cells have previously been found to destroy infected and cancerous cells. The team observed that CCL5 is expressed by cancer cells, while CXC9 is produced by myeloid immune cells such as macrophages and dendritic cells.
They observed cancer cells reduce their production of CCL5 also coincide with a reduction in CXCL9, which causes the progressive depletion of CD8+ T-cells in tumors. The loss of CCL5 expression correlates with a chemical modification of DNA, which inhibits the expression of targeted genes reports Drug Target Review.
The team’s findings lead to a conclusion that CCL5 and CXCL9 may become a useful biomarkers for immunotherapy. They can be used to identify patients whose tumors are infiltrated by activated T-cells and hence are more likely to be susceptible to immunotherapies, such as anti-PD1 antibodies.
Dr. George Coukos, director of the Lausanne Branch, Ludwig Institute for Cancer Research