Synergy of topical toll-like receptor 7 agonist with radiation and low-dose cyclophosphamide in a mouse model of cutaneous breast cancer
M Zahidunnabi Dewan, Claire Vanpouille-Box, Noriko Kawashima, Sara DiNapoli, James S Babb, Silvia C Formenti, Sylvia Adams, Sandra Demaria, M Zahidunnabi Dewan, Claire Vanpouille-Box, Noriko Kawashima, Sara DiNapoli, James S Babb, Silvia C Formenti, Sylvia Adams, Sandra Demaria
Abstract
Purpose: This study tested the hypothesis that topical Toll-like receptor (TLR) 7 agonist imiquimod promotes antitumor immunity and synergizes with other treatments in a model of skin-involving breast cancer.
Experimental design: TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice. Imiquimod 5% or placebo cream was applied topically on the shaved skin overlying tumors three times/wk. In some experiments, local ionizing radiation therapy (RT) was delivered to the tumor in three fractions of 8 Gy, given on consecutive days. Cyclophosphamide was given intraperitoneally (i.p.) in one dose of 2 mg/mouse. Mice were followed for tumor growth and survival.
Results: Treatment with imiquimod significantly inhibited tumor growth, an effect that was associated with increased tumor infiltration by CD11c(+), CD4(+), and CD8(+) cells, and abolished by depletion of CD8(+) cells. Administration of imiquimod in combination with RT enhanced significantly tumor response compared with either treatment alone (P < 0.005), and 11% to 66% of irradiated tumors completely regressed. Importantly, the addition of topical imiquimod also resulted in growth inhibition of a secondary tumor outside of the radiation field. Low-dose cyclophosphamide given before start of treatment with imiquimod and RT further improved tumor inhibition and reduced tumor recurrence. Mice that remained tumor-free rejected a tumorigenic inoculum of TSA cells, showing long-term immunologic memory.
Conclusions: Topical imiquimod inhibits tumor growth and synergizes with RT. Addition of cyclophosphamide further increases the therapeutic effect and induces protective immunologic memory, suggesting that this combination is a promising strategy for cutaneous breast cancer metastases.
2012 AACR.
Figures
![Figure 1. Topical imiquimod inhibits growth of…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3525760/bin/nihms-414102-f0001.jpg)
![Figure 2. RT and imiquimod synergize in…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3525760/bin/nihms-414102-f0002.jpg)
Figure 3. Topical imiquimod sensitizes a secondary…
Figure 3. Topical imiquimod sensitizes a secondary tumor to the abscopal effect induced by treatment…
Figure 4. Topical imiquimod upregulates MHC class…
Figure 4. Topical imiquimod upregulates MHC class I molecule and ICAM-1 on tumor cells and…
Figure 5. Low dose CY reduces Treg…
Figure 5. Low dose CY reduces Treg cells and IL-10 production, and enhances tumor-specific IFN-γ…
Figure 6. Low dose CY improves tumor…
Figure 6. Low dose CY improves tumor inhibition by IMQ+RT
(A) Treatment schema. (B) Tumor…
- Breast cancer treatment with imiquimod: applying an old lotion to a new disease.Kohrt H. Kohrt H. Clin Cancer Res. 2012 Dec 15;18(24):6571-3. doi: 10.1158/1078-0432.CCR-12-3138. Epub 2012 Nov 21. Clin Cancer Res. 2012. PMID: 23172886
- Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.Adams S, Kozhaya L, Martiniuk F, Meng TC, Chiriboga L, Liebes L, Hochman T, Shuman N, Axelrod D, Speyer J, Novik Y, Tiersten A, Goldberg JD, Formenti SC, Bhardwaj N, Unutmaz D, Demaria S. Adams S, et al. Clin Cancer Res. 2012 Dec 15;18(24):6748-57. doi: 10.1158/1078-0432.CCR-12-1149. Epub 2012 Jul 5. Clin Cancer Res. 2012. PMID: 22767669 Free PMC article. Clinical Trial.
- Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.Ito H, Ando T, Arioka Y, Saito K, Seishima M. Ito H, et al. Immunology. 2015 Apr;144(4):621-30. doi: 10.1111/imm.12413. Immunology. 2015. PMID: 25322876 Free PMC article.
- Breast cancer treatment with imiquimod: applying an old lotion to a new disease.Kohrt H. Kohrt H. Clin Cancer Res. 2012 Dec 15;18(24):6571-3. doi: 10.1158/1078-0432.CCR-12-3138. Epub 2012 Nov 21. Clin Cancer Res. 2012. PMID: 23172886
- Beyond a decade of 5% imiquimod topical therapy.A Gaspari A, Tyring SK, Rosen T. A Gaspari A, et al. J Drugs Dermatol. 2009 May;8(5):467-74. J Drugs Dermatol. 2009. PMID: 19537370 Review.
- [New perspective in immunotherapy: local imiquimod treatment].Kemény L, Nagy N. Kemény L, et al. Orv Hetil. 2010 May 9;151(19):774-83. doi: 10.1556/OH.2010.28866. Orv Hetil. 2010. PMID: 20427260 Review. Hungarian.
- Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control.Rodriguez-Ruiz ME, Serrano-Mendioroz I, Garate-Soraluze E, Sánchez-Mateos P, Barrio-Alonso C, Rodríguez López I, Diaz Pascual V, Arbea Moreno L, Alvarez M, Sanmamed MF, Perez-Gracia JL, Escuin-Ordinas H, Quintero M, Melero I. Rodriguez-Ruiz ME, et al. J Immunother Cancer. 2023 Jan;11(1):e005011. doi: 10.1136/jitc-2022-005011. J Immunother Cancer. 2023. PMID: 36631161 Free PMC article.
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Chan Wah Hak CML, Rullan A, Patin EC, Pedersen M, Melcher AA, Harrington KJ. Chan Wah Hak CML, et al. Front Oncol. 2022 Aug 29;12:971959. doi: 10.3389/fonc.2022.971959. eCollection 2022. Front Oncol. 2022. PMID: 36106115 Free PMC article. Review.
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.Rostamizadeh L, Molavi O, Rashid M, Ramazani F, Baradaran B, Lavasanaifar A, Lai R. Rostamizadeh L, et al. Bioimpacts. 2022;12(3):261-290. doi: 10.34172/bi.2022.23896. Epub 2022 Mar 26. Bioimpacts. 2022. PMID: 35677663 Free PMC article. Review.
- The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes.Lovelock DF, Liu W, Langston SE, Liu J, Van Voorhies K, Giffin KA, Vetreno RP, Crews FT, Besheer J. Lovelock DF, et al. Addict Biol. 2022 May;27(3):e13176. doi: 10.1111/adb.13176. Addict Biol. 2022. PMID: 35470561 Free PMC article.
- Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities.Huang S, Parekh V, Waisman J, Jones V, Yuan Y, Vora N, Li R, Jung J, Kruper L, Abdulla F, Fong Y, Li WY. Huang S, et al. J Surg Oncol. 2022 Aug;126(2):217-238. doi: 10.1002/jso.26870. Epub 2022 Apr 7. J Surg Oncol. 2022. PMID: 35389520 Free PMC article. Review.
- Administration, Topical
- Aminoquinolines / administration & dosage
- Animals
- Antineoplastic Combined Chemotherapy Protocols / adverse effects
- Antineoplastic Combined Chemotherapy Protocols / pharmacology
- Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
- Cell Line, Tumor
- Chemoradiotherapy
- Cyclophosphamide / administration & dosage
- Cytokines / metabolism
- Dose Fractionation, Radiation
- Drug Synergism
- Histocompatibility Antigens Class I / genetics
- Histocompatibility Antigens Class I / metabolism
- Humans
- Imiquimod
- Immunologic Memory
- Injections, Intraperitoneal
- Intercellular Adhesion Molecule-1 / genetics
- Intercellular Adhesion Molecule-1 / metabolism
- Lymph Nodes / drug effects
- Lymph Nodes / immunology
- Mammary Neoplasms, Experimental / drug therapy*
- Mammary Neoplasms, Experimental / immunology
- Mammary Neoplasms, Experimental / pathology
- Mammary Neoplasms, Experimental / radiotherapy
- Membrane Glycoproteins / agonists*
- Mice
- Mice, Inbred BALB C
- Neoplasm Recurrence, Local / prevention & control
- Neoplasm Transplantation
- Skin Neoplasms / drug therapy*
- Skin Neoplasms / immunology
- Skin Neoplasms / radiotherapy
- Skin Neoplasms / secondary
- T-Lymphocytes / drug effects
- T-Lymphocytes / immunology
- T-Lymphocytes / metabolism
- Toll-Like Receptor 7 / agonists*
- Tumor Burden / drug effects
- Tumor Burden / radiation effects
- Aminoquinolines
- Cytokines
- Histocompatibility Antigens Class I
- ICAM1 protein, human
- Membrane Glycoproteins
- Tlr7 protein, mouse
- Toll-Like Receptor 7
- Intercellular Adhesion Molecule-1
- Cyclophosphamide
- Imiquimod
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3. Topical imiquimod sensitizes a secondary…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3525760/bin/nihms-414102-f0003.jpg)
Figure 4. Topical imiquimod upregulates MHC class…
Figure 4. Topical imiquimod upregulates MHC class I molecule and ICAM-1 on tumor cells and…
Figure 5. Low dose CY reduces Treg…
Figure 5. Low dose CY reduces Treg cells and IL-10 production, and enhances tumor-specific IFN-γ…
Figure 6. Low dose CY improves tumor…
Figure 6. Low dose CY improves tumor inhibition by IMQ+RT
(A) Treatment schema. (B) Tumor…
- Breast cancer treatment with imiquimod: applying an old lotion to a new disease.Kohrt H. Kohrt H. Clin Cancer Res. 2012 Dec 15;18(24):6571-3. doi: 10.1158/1078-0432.CCR-12-3138. Epub 2012 Nov 21. Clin Cancer Res. 2012. PMID: 23172886
- Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.Adams S, Kozhaya L, Martiniuk F, Meng TC, Chiriboga L, Liebes L, Hochman T, Shuman N, Axelrod D, Speyer J, Novik Y, Tiersten A, Goldberg JD, Formenti SC, Bhardwaj N, Unutmaz D, Demaria S. Adams S, et al. Clin Cancer Res. 2012 Dec 15;18(24):6748-57. doi: 10.1158/1078-0432.CCR-12-1149. Epub 2012 Jul 5. Clin Cancer Res. 2012. PMID: 22767669 Free PMC article. Clinical Trial.
- Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.Ito H, Ando T, Arioka Y, Saito K, Seishima M. Ito H, et al. Immunology. 2015 Apr;144(4):621-30. doi: 10.1111/imm.12413. Immunology. 2015. PMID: 25322876 Free PMC article.
- Breast cancer treatment with imiquimod: applying an old lotion to a new disease.Kohrt H. Kohrt H. Clin Cancer Res. 2012 Dec 15;18(24):6571-3. doi: 10.1158/1078-0432.CCR-12-3138. Epub 2012 Nov 21. Clin Cancer Res. 2012. PMID: 23172886
- Beyond a decade of 5% imiquimod topical therapy.A Gaspari A, Tyring SK, Rosen T. A Gaspari A, et al. J Drugs Dermatol. 2009 May;8(5):467-74. J Drugs Dermatol. 2009. PMID: 19537370 Review.
- [New perspective in immunotherapy: local imiquimod treatment].Kemény L, Nagy N. Kemény L, et al. Orv Hetil. 2010 May 9;151(19):774-83. doi: 10.1556/OH.2010.28866. Orv Hetil. 2010. PMID: 20427260 Review. Hungarian.
- Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control.Rodriguez-Ruiz ME, Serrano-Mendioroz I, Garate-Soraluze E, Sánchez-Mateos P, Barrio-Alonso C, Rodríguez López I, Diaz Pascual V, Arbea Moreno L, Alvarez M, Sanmamed MF, Perez-Gracia JL, Escuin-Ordinas H, Quintero M, Melero I. Rodriguez-Ruiz ME, et al. J Immunother Cancer. 2023 Jan;11(1):e005011. doi: 10.1136/jitc-2022-005011. J Immunother Cancer. 2023. PMID: 36631161 Free PMC article.
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Chan Wah Hak CML, Rullan A, Patin EC, Pedersen M, Melcher AA, Harrington KJ. Chan Wah Hak CML, et al. Front Oncol. 2022 Aug 29;12:971959. doi: 10.3389/fonc.2022.971959. eCollection 2022. Front Oncol. 2022. PMID: 36106115 Free PMC article. Review.
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.Rostamizadeh L, Molavi O, Rashid M, Ramazani F, Baradaran B, Lavasanaifar A, Lai R. Rostamizadeh L, et al. Bioimpacts. 2022;12(3):261-290. doi: 10.34172/bi.2022.23896. Epub 2022 Mar 26. Bioimpacts. 2022. PMID: 35677663 Free PMC article. Review.
- The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes.Lovelock DF, Liu W, Langston SE, Liu J, Van Voorhies K, Giffin KA, Vetreno RP, Crews FT, Besheer J. Lovelock DF, et al. Addict Biol. 2022 May;27(3):e13176. doi: 10.1111/adb.13176. Addict Biol. 2022. PMID: 35470561 Free PMC article.
- Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities.Huang S, Parekh V, Waisman J, Jones V, Yuan Y, Vora N, Li R, Jung J, Kruper L, Abdulla F, Fong Y, Li WY. Huang S, et al. J Surg Oncol. 2022 Aug;126(2):217-238. doi: 10.1002/jso.26870. Epub 2022 Apr 7. J Surg Oncol. 2022. PMID: 35389520 Free PMC article. Review.
- Administration, Topical
- Aminoquinolines / administration & dosage
- Animals
- Antineoplastic Combined Chemotherapy Protocols / adverse effects
- Antineoplastic Combined Chemotherapy Protocols / pharmacology
- Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
- Cell Line, Tumor
- Chemoradiotherapy
- Cyclophosphamide / administration & dosage
- Cytokines / metabolism
- Dose Fractionation, Radiation
- Drug Synergism
- Histocompatibility Antigens Class I / genetics
- Histocompatibility Antigens Class I / metabolism
- Humans
- Imiquimod
- Immunologic Memory
- Injections, Intraperitoneal
- Intercellular Adhesion Molecule-1 / genetics
- Intercellular Adhesion Molecule-1 / metabolism
- Lymph Nodes / drug effects
- Lymph Nodes / immunology
- Mammary Neoplasms, Experimental / drug therapy*
- Mammary Neoplasms, Experimental / immunology
- Mammary Neoplasms, Experimental / pathology
- Mammary Neoplasms, Experimental / radiotherapy
- Membrane Glycoproteins / agonists*
- Mice
- Mice, Inbred BALB C
- Neoplasm Recurrence, Local / prevention & control
- Neoplasm Transplantation
- Skin Neoplasms / drug therapy*
- Skin Neoplasms / immunology
- Skin Neoplasms / radiotherapy
- Skin Neoplasms / secondary
- T-Lymphocytes / drug effects
- T-Lymphocytes / immunology
- T-Lymphocytes / metabolism
- Toll-Like Receptor 7 / agonists*
- Tumor Burden / drug effects
- Tumor Burden / radiation effects
- Aminoquinolines
- Cytokines
- Histocompatibility Antigens Class I
- ICAM1 protein, human
- Membrane Glycoproteins
- Tlr7 protein, mouse
- Toll-Like Receptor 7
- Intercellular Adhesion Molecule-1
- Cyclophosphamide
- Imiquimod
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 4. Topical imiquimod upregulates MHC class…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3525760/bin/nihms-414102-f0004.jpg)
![Figure 5. Low dose CY reduces Treg…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3525760/bin/nihms-414102-f0005.jpg)
Figure 6. Low dose CY improves tumor…
Figure 6. Low dose CY improves tumor inhibition by IMQ+RT
(A) Treatment schema. (B) Tumor…
- Breast cancer treatment with imiquimod: applying an old lotion to a new disease.Kohrt H. Kohrt H. Clin Cancer Res. 2012 Dec 15;18(24):6571-3. doi: 10.1158/1078-0432.CCR-12-3138. Epub 2012 Nov 21. Clin Cancer Res. 2012. PMID: 23172886
- Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.Adams S, Kozhaya L, Martiniuk F, Meng TC, Chiriboga L, Liebes L, Hochman T, Shuman N, Axelrod D, Speyer J, Novik Y, Tiersten A, Goldberg JD, Formenti SC, Bhardwaj N, Unutmaz D, Demaria S. Adams S, et al. Clin Cancer Res. 2012 Dec 15;18(24):6748-57. doi: 10.1158/1078-0432.CCR-12-1149. Epub 2012 Jul 5. Clin Cancer Res. 2012. PMID: 22767669 Free PMC article. Clinical Trial.
- Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.Ito H, Ando T, Arioka Y, Saito K, Seishima M. Ito H, et al. Immunology. 2015 Apr;144(4):621-30. doi: 10.1111/imm.12413. Immunology. 2015. PMID: 25322876 Free PMC article.
- Breast cancer treatment with imiquimod: applying an old lotion to a new disease.Kohrt H. Kohrt H. Clin Cancer Res. 2012 Dec 15;18(24):6571-3. doi: 10.1158/1078-0432.CCR-12-3138. Epub 2012 Nov 21. Clin Cancer Res. 2012. PMID: 23172886
- Beyond a decade of 5% imiquimod topical therapy.A Gaspari A, Tyring SK, Rosen T. A Gaspari A, et al. J Drugs Dermatol. 2009 May;8(5):467-74. J Drugs Dermatol. 2009. PMID: 19537370 Review.
- [New perspective in immunotherapy: local imiquimod treatment].Kemény L, Nagy N. Kemény L, et al. Orv Hetil. 2010 May 9;151(19):774-83. doi: 10.1556/OH.2010.28866. Orv Hetil. 2010. PMID: 20427260 Review. Hungarian.
- Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control.Rodriguez-Ruiz ME, Serrano-Mendioroz I, Garate-Soraluze E, Sánchez-Mateos P, Barrio-Alonso C, Rodríguez López I, Diaz Pascual V, Arbea Moreno L, Alvarez M, Sanmamed MF, Perez-Gracia JL, Escuin-Ordinas H, Quintero M, Melero I. Rodriguez-Ruiz ME, et al. J Immunother Cancer. 2023 Jan;11(1):e005011. doi: 10.1136/jitc-2022-005011. J Immunother Cancer. 2023. PMID: 36631161 Free PMC article.
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Chan Wah Hak CML, Rullan A, Patin EC, Pedersen M, Melcher AA, Harrington KJ. Chan Wah Hak CML, et al. Front Oncol. 2022 Aug 29;12:971959. doi: 10.3389/fonc.2022.971959. eCollection 2022. Front Oncol. 2022. PMID: 36106115 Free PMC article. Review.
- Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands.Rostamizadeh L, Molavi O, Rashid M, Ramazani F, Baradaran B, Lavasanaifar A, Lai R. Rostamizadeh L, et al. Bioimpacts. 2022;12(3):261-290. doi: 10.34172/bi.2022.23896. Epub 2022 Mar 26. Bioimpacts. 2022. PMID: 35677663 Free PMC article. Review.
- The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes.Lovelock DF, Liu W, Langston SE, Liu J, Van Voorhies K, Giffin KA, Vetreno RP, Crews FT, Besheer J. Lovelock DF, et al. Addict Biol. 2022 May;27(3):e13176. doi: 10.1111/adb.13176. Addict Biol. 2022. PMID: 35470561 Free PMC article.
- Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities.Huang S, Parekh V, Waisman J, Jones V, Yuan Y, Vora N, Li R, Jung J, Kruper L, Abdulla F, Fong Y, Li WY. Huang S, et al. J Surg Oncol. 2022 Aug;126(2):217-238. doi: 10.1002/jso.26870. Epub 2022 Apr 7. J Surg Oncol. 2022. PMID: 35389520 Free PMC article. Review.
- Administration, Topical
- Aminoquinolines / administration & dosage
- Animals
- Antineoplastic Combined Chemotherapy Protocols / adverse effects
- Antineoplastic Combined Chemotherapy Protocols / pharmacology
- Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
- Cell Line, Tumor
- Chemoradiotherapy
- Cyclophosphamide / administration & dosage
- Cytokines / metabolism
- Dose Fractionation, Radiation
- Drug Synergism
- Histocompatibility Antigens Class I / genetics
- Histocompatibility Antigens Class I / metabolism
- Humans
- Imiquimod
- Immunologic Memory
- Injections, Intraperitoneal
- Intercellular Adhesion Molecule-1 / genetics
- Intercellular Adhesion Molecule-1 / metabolism
- Lymph Nodes / drug effects
- Lymph Nodes / immunology
- Mammary Neoplasms, Experimental / drug therapy*
- Mammary Neoplasms, Experimental / immunology
- Mammary Neoplasms, Experimental / pathology
- Mammary Neoplasms, Experimental / radiotherapy
- Membrane Glycoproteins / agonists*
- Mice
- Mice, Inbred BALB C
- Neoplasm Recurrence, Local / prevention & control
- Neoplasm Transplantation
- Skin Neoplasms / drug therapy*
- Skin Neoplasms / immunology
- Skin Neoplasms / radiotherapy
- Skin Neoplasms / secondary
- T-Lymphocytes / drug effects
- T-Lymphocytes / immunology
- T-Lymphocytes / metabolism
- Toll-Like Receptor 7 / agonists*
- Tumor Burden / drug effects
- Tumor Burden / radiation effects
- Aminoquinolines
- Cytokines
- Histocompatibility Antigens Class I
- ICAM1 protein, human
- Membrane Glycoproteins
- Tlr7 protein, mouse
- Toll-Like Receptor 7
- Intercellular Adhesion Molecule-1
- Cyclophosphamide
- Imiquimod
- Full Text Sources
- Other Literature Sources
- Medical
- Research Materials
- Miscellaneous
![Figure 6. Low dose CY improves tumor…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3525760/bin/nihms-414102-f0006.jpg)
Source: PubMed