New cancer treatment re-engages the immune system to fight cancerous cells

Immunotherapy uses the body’s own immune system to fight cancer, but not all types of cancer can be treated with this treatment. MIT researchers have studied this therapy and found that treating removed tumor cells with chemotherapy drugs, which activates T cells within the body, then inserting them back into the tumor. Co-senior author of the study, Michael Yaffe, David H. Koch Professor of Science and the director of the MIT Center for Precision Cancer Medicine, commented that “when you create cells that have DNA damage but are not killed, under certain conditions those live, injured cells can send a signal that awakens the immune system”. When tested with mice, researchers discovered that tumors on nearly half of them were successfully removed.

Currently, cancer immunotherapy uses checkpoint blockade inhibitors that release T cells no longer able to attack tumors, but these drugs do not work for all types of cancer. In response, Yaffe and his colleagues combined the checkpoint blockade inhibitors with cytotoxic chemotherapy drugs, assuming that the drugs involve immunogenic cell death, or dead tumor cells signaling for the immune system. The study began the study with chemotherapy drugs on the cancer cells at different doses. Dendritic cells then T-cells were added to each dish of treatment, each after a 24-hour time frame. Researchers found, however, that the best results were shown when there were little to no chemotherapy drugs involved in the treatment.

They soon realized that rather than the dead tumor cells signaling to the immune system, it was the injured but alive tumor cells stimulating it. Therefore, the best drugs for treatment appeared to be those that damaged the DNA of tumor cells but did not kill them, as cellular pathways, which are the key responders of stress, are only active when the cells are alive. Through these pathways, T cells receive the signals to act against all injured cells, including those on a tumor. As a result, when researchers used this technique on mice with melanoma and breast tumors, it was completely withdrawn from the body of 40% of the mice. Additionally, their T-cells were able to recognize and kill cancerous cells when they were injected into the same mice that received the treatment before the cells could form new tumors.

Although this treatment is not effective when the drugs are directly injected into the tumors due to the damage inflicted on the T cells as well, Yaffe wishes to extend his research by presenting “something that can act as an immunostimulant”, which also happens to “release the preexisting block on the immune cells”. Researchers are also continuing their study on how injured tumor cells signal for T cell responses so that more patients with different types of cancer can be treated.


Categories: Clinical