Immunotherapy based on antibodies to PD-1 has been a major advance in the treatment of lung cancer. However, only 1 in 5 patients benefit from this therapy.

Researchers at Cima University of Navarra have developed an innovative experimental project that increases the therapeutic capacity of immunotherapy for the most common lung cancer (non-small cell). The results have been published in the first issue of the journal Nature Cancer.

Several programs of study suggest that fasting conditions reactivate antitumor immunity and improve the therapeutic capacity of chemotherapy. "Following this premise, we set out to determine the role of fasting in immunotherapy, and we confirmed that intermittent fasting cycles increase the antitumor capacity of anti-PD-1 in animal models of lung cancer," explains Dr. Daniel Ajona, researcher of the Solid Tumors Program at Cima and first author of work.

The scientists analyzed the molecular mechanisms governing this finding and found that "fasting decreases the levels of a molecule (IGF 1), which sensitizes tumor cells to treatment with anti PD-1-based immunotherapy".

Response to treatment

From agreement with this observation, the results suggest that lung cancer patients with elevated levels of circulating IGF-1 respond worse to anti-PD-1-based immunotherapy. "These findings could form the basis for evaluating, in the context of clinical trials, the ability of temporary fasting or IGF-1 inhibition to improve the performance of cancer immunotherapy," says Dr. Ruben Pio, director of the Solid Tumor Program at Cima.

The work has been carried out in the framework of the high school Sanitario de Navarra (IdiSNA) and the CIBER de Cáncer (CIBERONC) and has been financed by the high school de Salud Carlos III-Fondo de research Sanitaria-Fondo Europeo de development Regional 'Una manera de hacer Europa' (Cofinanciado Fondos FEDER; PI17/00411, PI16/01352, PI16/01821 and AC14/00034), the association Española contra el Cáncer (AECC), the Fundación Ramón Areces and la Caixa, among other public and private grants.

• reference letter bibliographic:
  https://www.nature.com/articles/s43018-019-0007-9