Tackling immunotherapy resistance

Despite its success, immunotherapy resistance poses a serious issue which negatively impacts patient outcomes. Resistance to immunotherapy can be divided into two types: intrinsic (primary) resistance, which is described as lack of initial response or clinical benefit to therapy, and acquired (secondary) resistance which is disease progression after an initial period of clinical benefit.

In contrast to targeted therapies, a majority of resistance to immune checkpoint inhibitors is due to intrinsic resistance. Currently, insights into mechanisms of acquired resistance to immune checkpoint inhibitors are limited. It is known that resistance can be mediated by tumour-related intrinsic and extrinsic factors and that for example loss of tumour neoantigens (e.g. chromosomal loss, defects in antigen processing) may mediate resistance in a subset of patients [1].

Various strategies and approaches are being evaluated, such as adding an oncolytic virus to immune checkpoint inhibitor treatment in naïve patients or adding a novel agent to immunotherapy in these patients. Combinations of a novel agent and immunochemotherapy in first-line non-small-cell lung cancer treatment in naïve patients is also assessed, as is addition of a targeted agent in treatment-experienced patients, as it is known that targeted therapy can modulate immune cell function. Furthermore, novel agents are thoroughly studies and evaluated to establish their possible role in overcoming resistance (see Table) [2].

Table. Overview of novel agents that may aid in overcoming resistance [2]

1. Gainor JF, et al. MS01.01. WCLC 2019.
2. Soo R, et al. MS01.03. WCLC 2019.

Posted on 8 November 20195 March 2021