Table 3.

Improving treatment outcomes to ICI and increasing the indication range

Drug combination	Target	Mechanism/Rational	Outcomes	Indications	Reference
ICI Radiotherapy	PD-1, PD-L1, CTLA-4 DNA	Induction of somatic mutations that can generate neoantigens, promotion of chemokines secretion that attract CD8+ T cells	Improved disease control and survival outcomes	NSCLC, RCC, HCC	32, 95, 96, 97, 98, 99
Spartalizumab Dabrafenib with Trametinib	PD-1 BRAF MEK1	BRAF inhibition reduces anti-inflammatory cytokine levels that suppress tumor-infiltrating lymphocytes (TILs)	High response rate and reduced relapse compared to BRAF-MEK inhibitor monotherapy	Melanoma	100, 101, 102, 103-105
Pembrolizumab Trastuzumab	PD-1 HER-2	Resistance to trastuzumab is characterized by upregulated PD-1/PD-L1 expression, thus, combination of trastuzumab with pembrolizumab can be beneficial	15% response rate in PD-L1-positive tumors and a 12-month PFS rate of 13%	Metastatic HER2-positive breast cancer, HER2-positive gastric adenocarcinoma	109, 110, 111, 112

Abbreviations: ICI immune checkpoint inhibitor, PD-1 programmed cell death protein 1, PD-L1 programmed death-ligand 1, CTLA-4 cytotoxic-T-lymphocyte-associated protein 4, NSCLC non small cell lung cancer, RCC renal cell carcinoma, HCC hepatocellular carcinoma, HER-2 human epidermal growth factor receptor 2, PFS progression-free survival.