* Adapted from Blank CU. et al., Science (2016)
Metabolic reprogramming such as adaptation to hypoxia and/or nutrient deprivation, confers a favorable contexture to the tumor as well as an impaired anti-tumor immunity caused by changes in the microenvironment. Some of these adaptations translate into specific peripheral biomarkers which have been shown to be associated with clinical outcome.
For example, upon immune checkpoint inhibition, high serum concentrations of lactate dehydrogenase (LDH) predicted poor outcome (Weide B. et al., 2016).
The biochemical nature of the tumor microenvironment can shape the immune contexture and in case of high inflammation, contribute to tumor progression by fostering immune evasion.
These pro-inflammatory signals (VEGF, CSF, interleukins) can emanate from the tumor itself or from accessory cells present in the microenvironment (such as subtype of neutrophils, δγ T cells, Cancer-Associated Fibroblasts and macrophages).
Inflammatory markers such as the C-reactive protein (CRP) or the interleukin-6 can be detected in the peripheral system and provide confirmation of tumor-associated inflammation (Oya Y. et al., 2017).
Baseline immunity, in combination with the infiltration status at the tumor site can provide a general assessment of the degree of immune response to be expected upon immunotherapy.
A special focus will be brought to lymphocytes, neutrophils and myeloid-derived suppressor cells which have all been linked to immunotherapy outcome in a variety of cancers (Ferrucci et al., 2016; Zaragoza et al., 2016).
