Innate immunity and inflammation: from Cancer to COVID-19

The immune system is an extremely complex orchestra. The immune system and the central nervous system are the two most complex set of cells, connections and mediators in our body. Alterations of immunity and inflammation represent a metanarrative of modern medicine, spanning from infectious diseases to cardiovascular pathology to cancer.

Inflammatory cells and mediators are a key component of the tumor microenvironment. A change in paradigm and dissection of accelerators and brakes of immunity have spearheaded the birth of cancer immunotherapy. COVID-19 has highlighted how little we know of immunity to microbial challenges. As for cancer, a better understanding of the interaction of immunity with SARS-CoV-2 is likely to pave the way to new diagnostic and therapeutic tools. Examples of the usage of bioinformatic/AI approaches to deconvolute the complexity of immunity will be discussed.

References

Balkwill F R, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet 357: 539-545 (2001).

Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 454(7203):436-44, (2008).

Mantovani A, Netea M. Trained Innate Immunity: epigenetics and Covid-19. New Engl J Med 383(11):1078-1080 (2020)

Brunetta E, Folci M, Bottazzi B, De Santis M, Gritti G, Protti A, Mapelli SN, Bonovas S, Piovani D, Leone R, My I, Zanon V, Spata G, Bacci M, Supino D, Carnevale S, Sironi M, Davoudian S, Peano C, Landi F, Di Marco F, Raimodi F, Gianatti A, Angelini C, Rambaldi A, Garlanda C, Ciccarelli M, Cecconi M, Mantovani A. Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19. Nat Immunol 22(1): 19-24, 2021.

Forni G, Mantovani A. COVID-19 vaccines: where we stand and challenges ahead. Cell Death Diff 28(2): 626-639, 2021.

Stravalaci M, Pagani I, Paraboschi EM, Pedotti M, Doni A, Scavello F, Mapelli SN, Sironi M, Varani L, Matkovic M, Cavalli A, Cesana D, Gallina P, Pedemonte N, Capurro V, Clementi N, Mancini N, Invernizzi P, Rappuoli R, Duga S, Bottazzi B, Uguccioni M, Asselta R, Vicenzi E, Mantovani A, Garlanda C. Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules. Nature Immunol. 23, 275–286, 2022.

Mantovani A, Allavena P, Marchesi F, Garlanda C. Macrophages as tools and targets in cancer therapy. Nature Rev. Drug Develop., in press.