Figure 7.

Monitoring metabolic mechanisms of resistance to immune checkpoint blockade therapy. The evaluation of longitudinal tissue and serum metabolomics at pretreatment, early-treatment, and progression time points and its integration with molecular, immune, and microbiome analyses might unveil potential metabolic mechanisms of therapeutic resistance to immune checkpoint blockade therapy. In vitro and in vivo validation of emerging clinical data and de novo discovery of cancer cells’ dependency on metabolic genes/networks that dictate responsiveness and resistance to immune checkpoint inhibitors using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) screen-based screenings, metabolism-targeting therapeutics, and/or precision nutrition approaches, could provide a strong rationale for metabolically overcoming resistance to cancer immunotherapy.