Alberto Mantovani is the Scientific Director of Humanitas Clinical and Research Centre and professor at Humanitas University. For his research activity he has received numerous national and international awards and recognitions, including the Robert Koch Award 2016 for the transversal impact on Medicine of his discoveries in the field of immunology.
- There have been four main recent achievements in tumour immunotherapy. First, the FDA approved pembrolizumab, an immune checkpoint inhibitor, an anti-PD-1 antibody, for a tissue/site agnostic indication. The antibody can be used in patients with advanced cancer independently from the histological type, provided that the tumour has a specific characteristic of genetic instability, namely microsatellite instability (microsatellite instability-high, MSI-H). Such an approval is unprecedented. The decision is based on a study that was published in Science last year. The FDA approval has a relevant impact on patients: there are 9 histological types of cancer that can be MSI-H; we are talking of a small but significant number of patients. Moreover, it shows that tumour immunology and tumour genomics are closely related, and this is an important perspective for the future.
- Second, for the first time a comparison in non-small cell lung cancer between chemotherapy and immunotherapy was conducted. According to results presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, immunotherapy was superior to chemotherapy. This sent out an essential signal: the future of cancer cure will rely on the combination of these approaches.
- Third, new evidence indicates that immunotherapy will be successfully exploited in hard-to-treat cancers. Some of the big killers, such as breast cancer and pancreatic cancer, have been refractory to immunotherapy so far. A study, recently published in the New England Journal of Medicine, showed an effect on progression-free survival of a combination of immune checkpoint inhibitors and chemotherapy in triple-negative breast cancer.
- Fourth, there is a new frontier, close to my heart, opening in immunotherapy. A paper was just published in the New England Journal of Medicine, accompanied by an editorial of mine, demonstrating that by removing a brake in myeloid cells – CD47, a “do not eat me” signal – in combination with an anti-CD20 monoclonal antibody, significant results were achieved in patients with B-cell lymphomas refractory to two lines of therapy. The hope is that this study will lead to the introduction of a new class of checkpoint inhibitors: drugs that reactivate or potentiate myeloid cells.
- We should not forget that only 1 out of 4 or 5 patients benefits from immunotherapy. The commitment for the future must be to identify these patients, both to guarantee the sustainability of immunotherapy and to avoid unnecessary toxicity to the patients. We will need to find therapies for those that do not respond to the existing ones. Finally, we will need therapeutic strategies for the tumours that to date proved to be refractory to the immunotherapy approach, such as pancreatic cancer, breast cancer and colon cancer.
- Immunotherapy is today one of the most important fields of study in the search for anticancer therapies. Many medical oncologists stopped believing in cancer immunotherapy several years ago, nevertheless immunologists kept believing. The successes that have been reached are solely due to basic research. The crucial step was the discovery by Pierre Golstein of CTLA-4 and its identification as a checkpoint in cancer by James P Allison. A similar pathway, from fundamental immunology to cancer immunotherapy was followed by Tasuku Honjo, one of the winners of the 2018 Nobel prize in Medicine, for PD-1. The birth of cancer immunotherapy has its roots in a fundamental dissection of immunological mechanisms, without screening millions of compounds. There is no doubt that the world of immunotherapy is the result of basic research.