Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors

Abstract

Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding the transformation from 'cold' to 'hot' tumors is essential in developing effective cancer treatments. Furthermore, tumor immune profiling is critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success of immunotherapy relies on T cells' ability to recognize and eliminate tumor cells. In 'cold' tumors, the absence of T cell infiltration leads to the ineffectiveness of ICI therapy. Addressing these challenges, especially the impairment in T cell activation and homing, is crucial to enhance ICI therapy's efficacy. Concurrently, strategies to convert 'cold' tumors into 'hot' ones, including boosting T cell infiltration and adoptive therapies such as T cell-recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, are under extensive exploration. Thus, identifying key factors that impact tumor T cell infiltration is vital for creating effective treatments targeting 'cold' tumors.

Keywords: cold tumors; immune checkpoint inhibitors; immunotherapy; tumor microenvironment; tumor-infiltrating T lymphocytes.

Figure 1

A therapeutic strategy to convert cold tumors into hot tumors based on tumor immune cycle. The cancer-immunity cycle encapsulates seven pivotal steps, with each one being integral to the overall mechanism. A malfunction or inefficiency at any juncture can potentially instigate the tumor to evade the immune response. Nevertheless, a wide array of therapeutic approaches such as Chimeric Antigen Receptor T-cell (CAR-T) therapy, T-cell Redirecting Bispecific Antibodies, cancer vaccines, oncolytic viruses, macrophage-targeted therapies, radiotherapy, chemotherapy, targeted therapies, and nanoparticle-assisted treatments manifest their potential to modulate this cycle, thereby amplifying the body’s defensive reaction against tumors.