Table 1.

Overview of the immunologic findings in preclinical context of the combinatorial use of metronomic chemotherapy and immune checkpoint inhibitors.

Refs.	Treatment Drugs mCT + ICI	Tumor Type	Immunologic Outcome	Efficacy
[106]	Cyclophosphamide + anti-PD-1	Triple negative breast cancer	No increase of PD-1 or CD4+/CD8+ T cell	Not reported
[47]	Cisplatin/docetaxel + anti-PD-1	Squamous cell lung carcinoma	Increased macrophage Increased TIL (CD45+, CD3+, CD8+)	Not reported
[108]	Carboplatin + anti-PD-1	Lung cancer	Increased PD-1 expression Increased CD8+ T cell infiltration	Reduced tumor growth No adverse effect (mice body weight)
[101]	Gemcitabine + anti-PD-L1	Squamous cell lung carcinoma	Increased M1-like macrophage Increased CD8+ T cell infiltration Decreased M2-like macrophage	Complete inhibition of tumor growth
[109]	Multipeptide vaccine + XX+ anti-PD-1	Melanoma	Decreased Treg Increased INF-γ	Complete tumor inhibition
[110]	Gemcitabine + anti-PD-1	Lung cancer	Increased CD8+ T cell Decreased IL-10 Decreased Treg	Milder leucopenia Highest antitumor efficacy

mCT, metronomic chemotherapy; ICI, immune checkpoint inhibitors; PD-1, programmed death protein-1; TIL, tumor infiltrating lymphocytes; INF-γ, interferon-gamma; Treg, T regulatory cell; IL, interleukin.