A joint research of Cima University of Navarra and Yale University (USA) has discovered one of the causes of resistance to immunotherapy in lung cancer. The study identifies an alteration Genetics that modifies the tumor microenvironment and reduces the response to treatment in patients with this alteration.

The use of immune checkpoint inhibitors has dramatically changed the treatment of lung cancer. However, a significant issue of patients do not respond adequately to immunotherapy, so it is necessary to delve deeper into the causes of this lack of response.

"The absence of the PTEN tumor suppressor gene has been associated with resistance to immunotherapy in some types of cancer, such as melanoma and prostate cancer. In this work we show that it also affects the response to treatment of non-small cell lung cancer, the most common lung tumor," explains Dr. Alfonso Calvo, researcher of the Solid Tumor Program at Cima University of Navarra, part of the Cancer Center Clínica Universidad de Navarra, and director of work.

Tumor microenvironment

According to Fran Expósito, first author of the publication and current researcher postdoctoral fellow at Yale University (USA), "this study confirms that loss of PTEN is associated with the establishment of an immunosuppressive microenvironment that increases the infiltration of regulatory T cells and leads to a lack of response to anti-PD-1 therapy". The results of this work, performed on patient samples and animal models of lung cancer, have been featured on the cover of the journal Cancer Research.

"Thanks to these data, we have developed a therapeutic strategy based on the stimulation of the innate immune system that is capable of curing 100% of these immunotherapy-resistant tumors in an animal model ," the researchers note.

The next step is to establish more models of lung cancer with PTEN mutations to determine whether this therapy is as effective in other tumor contexts and thus evaluate the possibility of transferring it to the clinical field.           

The work, carried out at the framework of the research center Biomedica en network en Cáncer (CIBERONC), has received funding from public and private institutions such as the Ministry of Science and Innovation, the Government of Navarra, the association Española contra el Cáncer, the Ramón Areces Foundation and the "la Caixa" Foundation.

reference letter bibliographic

• Cancer Research. 2023 Aug 1;83(15):2513-2526.

PTEN Loss Confers Resistance to Anti-PD-1 Therapy in Non-Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells