Clonal tcell expansion

As many of you know, immunotherapies have been the latest discovery in the fight against cancer allowing patients to have a real complete regression sustained over time. Nowadays, there are more than 10,000 ongoing clinical trials. However, there is still plenty to discover about the underlying mechanisms.

It is fair to say that most of us though that upon PD-1 blockade (inhibitory checkpoint receptors on T cells), already existing T cells were able to infiltrate the tumor and destroy cancer cells. However, a recent publication in Nature Medicine by the group of H. Chang at Stanford University named “Clonal replacement of tumor-specific T cells following PD-1 blockade” has come up with a very interesting concept.

In this outstanding publication, Hang et al. have performed paired single-cell RNA seq and T cell receptor (TCR)-sequencing in different human tumors before and after anti PD-1 therapy. What they have observed is that present T cells are already exhausted and they are not capable to fight against cancer cells; they are dysfunctional. Instead, they have found a clonal expansion of CD8+CD39+ T cells but, what makes it really interesting is the fact that this clonal expansion is not coming from the T cells that were already there; they are coming from a new batch of T cells that may have arrived recently. And, these newly cloned T cells are the ones responsible for the antitumoral effect observed upon PD-1 blockade.

Immunotherapy has given us a new way to focus on cancer treatment, but obviously we still have a long way to go if we want to understand how this mechanism works.