The second presentation was about hyper-progressive disease. It was a session organised by AACR together with the FDA because several clinicians observed not just in non-small cell lung cancer but in other diseases that in a percentage of patients there is the sensation that the immunotherapy is able to increase the tumour growth. So the world is divided into believers and non-believers: the non-believers are people who think that this is just the representation of a more aggressive disease and the group of people who are convinced that there is a group of patients in which you can have an acceleration of the tumour growth. So there was an interesting panel of people who work behind this phenomenon; in our institute we work a lot behind this phenomenon. We found a particular immune phenotype which is an immunophenotype characterised by macrophages with an epithelioid morphology co-expressing PD-L1, CD33 and CD163 and expressed in all patients in which we think that this phenomenon can exist. So we are working on a prospective trial to test this phenomenon.

In parallel the preclinical laboratories of our institute reproduced the phenomenon or an increase of tumour growth in some animal models with the same genotype in which we observed the phenomenon in humans. We think that behind the phenomenon the innate immunity is involved and there is a switching of the macrophages from M1 to M2 through the FC portion of the immune checkpoint inhibitors. We are not totally sure about the mechanism, also the tumour can play a role with the PD-L1 expression on the tumour cells but we are working on that.

Anyway, in the panel it was very important because we thought that it was very important to harmonise the criteria to define what hyper-progressive disease is because every group is calling hyper-progressive disease with different criteria.