The final frontier in the fight against cancer is therapies that arm the patient's immune system so that it can recognise and kill cancer cells. What happens if the immune system has a defect? In this case, it is very likely that a mechanism of resistance to the immunotherapy used against the tumour will be triggered, seriously compromising the effectiveness of the treatment.

The presence of autoantibodies can be an alarm bell of a dysfunctional immune system, and the identification of biomarkers of this system can be a guide to choosing the correct therapy for the patient.

Marianna Nuti of the Department of Experimental Medicine of Sapienza, together with Paolo Marchetti and Guido Valesini, from the Oncology Unit B and the Rheumatology Centre of Policlinico Umberto I General Hospital respectively, have recently published a paper on the journal EBioMedicine, by The Lancet group, in which they investigate the role of an autoantibody in predicting early disease progression in patients with lung cancer treated with immunotherapy.  Researchers have seen that the presence of an autoantibody, called IgM-FR (class IgM rheumatoid factor), is associated, in patients with lung cancer, with the reduction of a specific population of immune cells, the antitumour T lymphocytes CD137⁺. This lymphocyte population is also one of the therapeutic targets of immunotherapy, so its reduction could result in a loss of treatment efficacy and a tendency to develop early disease progression within 3 months of initiation.

"Treatments with Immune Checkpoint Inhibitors, such as the anti-PD-1 immunotherapy, have greatly improved treatment options and outcome for cancer patients with Non-Small Cells Lung Cancer (NSCLC)", says Marianna Nuti, study coordinator. "However, many of these show resistance to therapy, which proves to be less effective: our work allows us to correlate part of the resistance with the presence of the IgM-FR autoantibody, which seems to bind to two classes of T lymphocytes, naïve and central memory, reducing their ability to traffick towards the tumor draining lymph nodes to be finally activated against cancer cells."

The results obtained with this study make it possible to take another step towards personalised medicine where it is the patient with his or her immune system that guides the choice of the best therapeutic approach, rather than the tumour and stage of illness.

Riferences:

IgM-Rheumatoid factor confers primary resistance to anti-PD-1 Immunotherapies in NSCLC patients by reducing CD137+ T-cells – Alessio Ugolini, Ilaria Grazia Zizzari, Fulvia Ceccarelli, Andrea Botticelli, Tania Colasanti, Lidia Strigari, Aurelia Rughetti, Hassan Rahimi, Fabrizio Conti, Guido Valesini, Paolo Marchetti, Marianna Nuti. – EBioMedicine - The Lancet, 2020. DOI https://doi.org/10.1016/j.ebiom.2020.103098

Further Information

Marianna Nuti
Department of Experimental Medicine
marianna.nuti@uniroma1.it