Table 4. Clinical applications of TLR7 agonists in cancer immunotherapy .
| TLR | Agonist | Combination | No. of samples | Cancer type | Response | Ref./The year |
|---|---|---|---|---|---|---|
| 7 | IMQ | - | 14 | Lung, colon, ovarian, melanoma, carcinoid, renal cell, breast, mesothelioma, chondrosarcoma, rectal, pancreatic | Induction of IFN-α, β-microglobulin and neopterin | 168 (1993) |
| 7 | IMQ | Flt3 ligand and tumor antigens | 8 | Metastatic melanoma | Developing both cutaneous and peptide-specific CD8+ T-cell responses | 182 (2004) |
| 7 | IMQ | - | 7 | BCC | Increasing mDCs and pDCs | 172 (2007) |
| 7 | IMQ | Recombinant NY-ESO-1 | 9 | Melanoma | Stimulation of humoral and cellular responses and IFNγ-secreting NY-ESO-1-specific CD4+ T cells | 46 (2008) |
| 7 | IMQ | Therapeutic HPV vaccination | 19 |
VIN associated with HPV16 infection |
Altering the balance of useful CD4+- and CD8+-directed effector cells | 185 (2010) |
| 7 | IMQ | - | 10 | Breast cancer skin metastases | Tumor regression, lymphocytic infiltrate and production of cytokines | 175 (2012) |
| 7 | IMQ | - | 8 | Breast cancer skin metastases | Upregulation of gene-related with Th1/cytotoxic immune response, migration of Th-1 and CTLs into the tumor, | 178 (2019) |
| 7 | IMQ | - | 11 | BCC | Increasing infiltration of the mononuclear inflammatory cell in the TME, decreasing the Bcl-2 | 173 (2009) |
| 7 | IMQ | - | 6 | BCC | Increasing apoptosis through downregulation of Bcl-2 expression | 169 (2003) |
| 7 | IMQ | - | 1 | Melanoma skin metastases | Upregulation of IFN-α, TIMP-1 and KiSS-1, MMP-1, and THBS1 downregulation of MMP-9, FGF2 | 177 (2004) |
| 7 | IMQ | - | 30 | BCC | Decreasing Bcl-2 expression and an increase in the apoptotic index | 171 (2004) |
| 7 | IMQ | Multipeptide cancer vaccine | 4 | Melanoma | Activation of T CD8+ and NK cells and infiltration in the TME | 184 (2016) |
| 7 | IMQ | - | 10 | BCC | Expression of FasR and increasing of T-lymphocytes | 170 (2003) |
| 7 |
Resiquimod (Topical) |
- | 12 | CTCL | Increasing T-cell clones, T-cell effector, NK cells, and circulating DCs functions | 179 (2015) |
| 7 |
Resiquimod (Topical) |
NY-ESO-1 and Montanide | 3 | Melanoma | Induction both specific humoral and CD4+ T-cell responses | 139 (2015) |
| 7 | 852A | - | 25 | Advanced cancer | Production of IFN-a, cytokine increasing, immunologic activity, and clinical symptoms | 180 (2007) |
| 7 | 852A | - | 13 | CT-refractory metastatic melanoma | Increasing of IP-10 and IFN-α and Th-1 cytokines (IFN-γ) | 186 (2008) |
| 7 | 852A | - | 15 | CLL | Increasing of TNF-α, Il-6, INF-α, and IgM | 136 (2010) |
| 7 or 3 | IMQ or poly-ICLC | Autologous tumor lysate and DC vaccine | 23 | Glioblastoma | Activation of DC, trafficking to lymph nodes, and the priming of anti-tumor antigen-specific T lymphocytes | 183 (2011) |
Abbreviations: CTCL: Cutaneous T-cell lymphoma; CLL: Chronic lymphocytic leukemia; BCC: Basal cell carcinoma; VIN: Vulval intraepithelial neoplasia; HPV: Human papillomavirus; mDC: myeloid dendritic cells; pDC: plasmacytoid dendritic cells; TLRs: Toll-like receptors; DC: Dendritic cell; Th-1: T helper cells; CTL: Cytotoxic T lymphocytes; IFN: Interferon-α; TNF-α: Tumor necrosis factor; (polyA:U); Poly-ICLC: poly-l-lysine and carboxymethylcellulose; IMQ: Imiqiumod; NY-ESO-1: New York esophageal squamous cell carcinoma 1; Flt3: fms like tyrosine kinase 3; Bcl-2: B-cell lymphoma 2; TIMP-1: Tissue inhibitor matrix metalloproteinase 1; KiSS-1: Kisspeptins; MMP: Matrix metallopeptidases; THBS1: Thrombospondin-1; FGF2: fibroblast growth factor; IP-10: Interferon gamma-induced protein 10.