Strategies to overcome resistance to immune checkpoint blockade in lung cancer

Abstract

The adoption of Immune checkpoint inhibitors (ICIs) allowed the achievement of impressive long-term survival results in non-small cell lung cancer (NSCLC), but most patients develop resistance to ICI treatment over time. Resistance to ICIs is mediated by several complex mechanisms affecting, but not limited to, tumour cell-intrinsic alterations and the tumour microenvironment. The possibility of modulating the immune response by interfering with specific alternative immune receptors, pathways and mediators might provide additional strategies to delay or prevent the development of resistance. Therefore, a greater in-depth investigation and understanding of these mechanisms aims to identify novel classes of immune targets and subsequently to evaluate potential new strategies for overcoming resistance, which will be assessed in this review.

Keywords: Adoptive cell therapy; Gut microbiota; Immunotherapy; Resistance mechanisms; TIGIT; Tumour microenvironment.