5.2.4. Tumoral Microenvironment as Biomarker

An important biomarker within the TME is tumour infiltrating immune cells. Tumours with effector T cell infiltration have an active immune microenvironment and respond better to immunotherapy [282]. Phenotypically, two classes of TME can be distinguished: those with a high prevalence of T cells and those without T cells [307].

Inflamed T-cell tumours have large numbers of T cells in the tumour periphery, plus increased expression of T-cell activation markers, type 1 interferons, and high levels of Th1 cytokines that recruit T cells. Because the cells that promote antitumour immunity are CD8+ T cells, CD4+ Th1 cells, NK cells, and mature DCs, tumours that have this predominant infiltration pattern respond better to antitumour immunotherapy [282]. Although tumour infiltrating lymphocytes are sometimes dysfunctional, their presence indicates that there is no inhibition of recruitment [294].

Tumours with a non-inflammatory T-cell microenvironment have few or no effector T cells, but contain chronic inflammation with tumour-associated macrophages, MDSCs, CD4 + FoxP3 + regulatory T cells, and Th2 cytokines, which form an immunosuppressed microenvironment that allows tumour progression, which is associated with a poorer prognosis.

Factors that may mediate the type of phenotype presented by the TME include some soluble and tumour-derived cell-membrane factors, but the mechanisms are not yet known [282].

The prognostic importance of T cells has been seen in some solid tumours, including colorectal, hepatocellular, pancreatic, esophageal, ovarian, non-small cell lung, brain metastases, melanoma, and head and neck cancer [282,294].

Antigen-specific T-cell recognition by MHC class I tetramer staining in situ or analysis of TCR's Vβ repertoire are used to characterise MSD T cells for their specificity [308,309]. Advances in multiplex IHC technologies in tumour tissue also provide information on the nature of immune infiltration into the tumour, depending on the type, number and qualitative characteristics of the immune cells present, and their interaction with tumour and stromal cells, which is related to disease progression and prognosis [294]. In biopsies from patients who respond favourably to checkpoint inhibition, they have a higher number of proliferating CD8+ T cells associated with high levels of expression of PD-L1 as assessed by IHC and higher expression of IFNγ as determined by the gene expression profile [310,311].
