Table 2.

Selected preclinical studies investigating de novo resistance mechanisms

Study	Study design	Findings
Grasso et al.33	Tumour samples of MSI-H patients (n = 179) underwent tumour exome, transcriptome, methylation, and copy-number alteration analyses	Multiple genetic alterations in antigen-presenting machinery including biallelic losses of β2M and HLA genes. GAs were also detected in pathways involving NK cell functions, T-cell response, B-cell development. Upregulated WNT signalling correlated with the absence of T-cell infiltration in the tumour microenvironment.
Riaz et al.38	Transcriptome analysis on samples from melanoma patients who received nivolumab therapy	Pre-existing CD8+ T-cell clones in the tumour microenvironment predicts response to nivolumab.
Herbst et al.39	Immunohistochemical and immunofluorescence evaluation of multiple cancers including two colorectal patients who received atezolizumab	Anti-PD-1 therapy is most effective when the pre-existing immune response is present including TH type1
Li et al.41	The computational method was performed to identify the complementarity-determining region 3 sequences of tumour-infiltrating T cells in 9142 RNA-seq samples across 29 cancer types	T-cell diversity correlates with tumour mutation burden and immune response
Michel et al.47	Immunohistochemical and immunofluorescence for evaluation of Foxp3 T-cell and CD8+ cell infiltration in MSI-H and MSS CRC patients	Increased number of CD8-FOXP3+ cells found in MSI-H colorectal cancers is paralleled to enhanced CD8-positive lymphocytes to counterbalance the immune response against cancer cells

MSI-H Microsatellite instability high, MSS Microsatellite stable, Anti-PD-1 Anti-programmed death 1