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OncoImmunology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/koni20
AMD3100 protects from UV-induced skin cancer abc
Scott N Byrne
& Seri NE Sarchio
abcd
a
Cellular Photoimmunology Group; Discipline of Infectious Diseases and Immunology; Sydney Medical School; University of Sydney; Sydney, NSW Australia b
Department of Dermatology; Royal Prince Alfred Hospital; Camperdown, NSW Australia
c
Discipline of Dermatology at The Bosch Institute; Sydney Medical School; University of Sydney; Sydney, NSW Australia d
Faculty of Medicine and Health Sciences; Universiti Putra Malaysia; Malaysia Published online: 03 Jan 2014.
Click for updates To cite this article: Scott N Byrne & Seri NE Sarchio (2014) AMD3100 protects from UV-induced skin cancer, OncoImmunology, 3:2, e27562, DOI: 10.4161/onci.27562 To link to this article: http://dx.doi.org/10.4161/onci.27562
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor & Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions It is essential that you check the license status of any given Open and Open Select article to confirm conditions of access and use.
Author’s View
Paper Type
OncoImmunology 3, e27562; January 2014; © 2014 Landes Bioscience
AMD3100 protects from UV-induced skin cancer Scott N Byrne1,2,3,* and Seri NE Sarchio1,2,3,4 2
1 Cellular Photoimmunology Group; Discipline of Infectious Diseases and Immunology; Sydney Medical School; University of Sydney; Sydney, NSW Australia; Department of Dermatology; Royal Prince Alfred Hospital; Camperdown, NSW Australia; 3Discipline of Dermatology at The Bosch Institute; Sydney Medical School; University of Sydney; Sydney, NSW Australia; 4Faculty of Medicine and Health Sciences; Universiti Putra Malaysia; Malaysia
Downloaded by [Georgian Court University] at 03:04 01 February 2015
Keywords: chemokines, mast cells, skin cancer, immunosuppression, sunlight, ultraviolet radiation
Sunlight causes skin cancer by directly damaging DNA as well as by suppressing antitumor immune responses. A major mechanism whereby sunlight exerts immunosuppressive effects is by modulating the migration of chemokine (C-X-C motif) receptor 4 (CXCR4)-expressing dermal mast cells into and away from the skin. We have demonstrated the importance of this by showing that the systemic administration of the CXCR4 antagonist AMD3100 prevents sunlightinduced immunosuppression as well as the consequent carcinogenic response. Our results highlight the therapeutic potential of antagonizing CXCR4 signaling, especially in individuals who are at high risk of developing skin cancer.
Skin cancer is a growing clinical and economic problem that is primarily caused by the excessive exposure to the ultraviolet (UV) component of sunlight. In patients with severe sun damage as well as in solid organ transplant recipients (which are under immunosuppressive regimens), UV-induced squamous cell carcinoma (SCCs) is particularly aggressive and is associated with an extremely poor prognosis. Indeed, the SCCs that develop in these patients are not only more numerous than those arising in immunocompetent individuals, but also more likely to disseminate to distant organs. The successful prevention and treatment of these aggressive skin cancers require equally aggressive prevention strategies and therapeutic interventions. In turn, this requires a thorough understanding of the cellular and molecular mechanisms by which UV promotes the development of cutaneous malignancies. In addition to damaging the DNA of our skin, UV also suppresses antitumor immune responses.1 As both these events contribute to skin carcinogenesis, inhibiting either of them could reduce the incidence of skin cancer, particularly among high-risk individuals. The cellular and molecular events triggered by UV exposure converge on the activation of regulatory cells that suppress
inflammation and adaptive immune responses.1 A critical player in this process is the dermal mast cell. While traditionally associated with atopic reactions, mast cells release anti-inflammatory cytokines that enable them to perform important immunoregulatory and anti-inflammatory functions. Indeed, the production of interleukin (IL)-10 by mast cells is required to prevent an excessive cutaneous inflammation in response to UV exposuure.2 As a matter of fact, UV rays do not exert immunosuppressive effects in mast cell-deficient Wf /Wf 3 or KitWSh/W-Sh mice,4 whereas the re-engraftment of mutant mice with wild-type bone marrow-derived mast cells restores the ability of UV to suppress adaptive immunity3,4. We provided mechanistic insights into this process by demonstrating that dermal mast cells activated by UV rays migrate along a chemokine (C-X-C motif) ligand 12 (CXCL12) gradient that attracts them to nodal lymphocytes in a chemokine (C-X-C motif) receptor 4 (CXCR4)-dependent manner. This cellular rendezvous is a critical event because pharmacologically blocking the trafficking of mast cells to the lymph nodes by means of CXCR4 antagonist AMD3100 blocked the immunosuppressive effects of UV irradiation.4
AMD3100 (Plerixafor, trade name Mozobil®) has recently been approved for mobilizing hematopoietic stem cells in hematological cancer patients prior to autologous transplantation. AMD3100 has also been shown to efficiently inhibit the growth of murine ovarian cancer5 as well as the metastatic dissemination of murine melanoma.6 The ability of AMD3100 to block the migration of mast cells has been linked to its capacity to suppress the growth of murine pancreatic ductal adenocarcinoma.7 Considering the central role that the migration of mast cells as induced by UV rays and the consequent immunosuppression play in skin carcinogenesis, we hypothesized that pharmacologically antagonizing CXCR4 with AMD3100 would also prevent UV-induced skin cancer. Indeed, we have recently demonstrated that this novel CXCR4 antagonist significantly protects mice from the development of sunlight-induced SCCs.8 The ability of AMD3100 to protect mice from chronic UV exposure-induced immunosuppression and carcinogenesis was associated with the inhibition of mast cell trafficking to the skin, the developing tumor and tumor-draining lymph nodes (Fig. 1). Orally supplied AMD3100 failed to affect peripheral
*Correspondence to: Scott Byrne; Email: [email protected] Submitted: 12/12/2013; Accepted: 12/17/2013; Published Online: 01/03/2014 Citation: Byrne SN, Sarchio SN. AMD3100 protects from UV-induced skin cancer. OncoImmunology 2013; 2:e27562; http://dx.doi.org/10.4161/onci.27562
www.landesbioscience.com OncoImmunology
e27562-1
Downloaded by [Georgian Court University] at 03:04 01 February 2015
Figure 1. Systemic treatment with the CXCR4-antagonist AMD3100 significantly protects from sunlight-induced skin cancer by modulating mast cell migration. The exposure of mice to 30 wk of sun-simulating UV (UVA + UVB) light resulted in the development of histopathologically confirmed squamous cell carcinomas (SCCs) associated with elevated levels of chemokine (C-X-C motif) receptor 4 (CXCR4). This was associated with a significant accumulation of mast cells not just into the irradiated dermis, but also into neoplastic lesions and tumor-draining lymph nodes. Such an alteration of the migratory pattern of mast cells did not occur in mice continually supplied with AMD3100 in the drinking water. Moreover, AMD3100-receiving mice were protected from the immunosuppressive effects of UV light and developed very few SCCs.
blood leukocytes, as well as any of the other CXCR4-expressing cells we investigated, including Ly6a + endothelial progenitor cells, FOXP3 + regulatory T cells and myofibroblasts expressing α-smooth muscle actin. Our findings have prominent clinical and societal implications. Indeed, although minimizing sun exposure is a useful strategy to reduce the incidence of skin cancer, this public health approach has failed to make a substantial dint in statistics. Perhaps, this is because we do not know the extent to which sun exposure would have to be decreased for the
e27562-2
incidence of skin cancers to decrease. Genetic mutations and immunosuppression are both caused by less than half of the sunburning dose of sunlight,9 but the dose that promotes skin carcinogenesis in humans is unknown. The healthpromoting effects of sunlight such as vitamin D production coupled to occupational and recreational activities might make it difficult to reduce cumulative sun exposure below a level that would substantially reduce the incidence of skin cancer, even with the use of sunscreens. Compelling evidence indicating that pharmacological strategies to prevent UV
OncoImmunology
exposure-induced immunosuppression can protect humans from skin cancer has already been provided.10 Our data demonstrating that AMD3100 can prevent primary UV-induced skin cancers by selectively interfering with the ability of UV rays to modulate mast cell trafficking and consequent immunosuppression8 highlight the chemopreventive (and perhaps therapeutic) potential of antagonizing the CXCL12/CXCR4 signaling axis. Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Volume 3
References
Downloaded by [Georgian Court University] at 03:04 01 February 2015
1.
Ullrich SE, Byrne SN. The immunologic revolution: photoimmunology. J Invest Dermatol 2012; 132:896905; http://dx.doi.org/10.1038/jid.2011.405; PMID:22170491 2. Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 2007; 8:1095-104; http://dx.doi.org/10.1038/ni1503; PMID:17767162 3. Hart PH, Grimbaldeston MA, Swift GJ, Jaksic A, Noonan FP, Finlay-Jones JJ. Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice. J Exp Med 1998; 187:2045-53; http://dx.doi. org/10.1084/jem.187.12.2045; PMID:9625764 4. Byrne SN, Limón-Flores AY, Ullrich SE. Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression. J Immunol 2008; 180:4648-55; PMID:18354188
5. Righi E, Kashiwagi S, Yuan J, Santosuosso M, Leblanc P, Ingraham R, Forbes B, Edelblute B, Collette B, Xing D, et al. CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res 2011; 71:5522-34; http:// d x.doi.org /10.1158 / 0008 -5472.C A N-10 -3143 ; PMID:21742774 6. D’Alterio C, Barbieri A, Portella L, Palma G, Polimeno M, Riccio A, Ieranò C, Franco R, Scognamiglio G, Bryce J, et al. Inhibition of stromal CXCR4 impairs development of lung metastases. Cancer Immunol Immunother 2012; 61:1713-20; http://dx.doi. org/10.1007/s00262-012-1223-7; PMID:22399057 7. Ma Y, Hwang RF, Logsdon CD, Ullrich SE. Dynamic mast cell-stromal cell interactions promote growth of pancreatic cancer. Cancer Res 2013; 73:3927-37; http://dx.doi.org/10.1158/0008-5472.CA N-124479; PMID:23633481
8. Sarchio SNE, Scolyer RA, Beaugie C, McDonald D, Marsh-Wakefield F, Halliday GM, Byrne SN. Pharmacologically antagonizing the CXCR4CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer. J Invest Dermatol 2014; 134:1091-100; http://dx.doi.org/10.1038/ jid.2013.424; PMID:24226205 9. Halliday GM, Damian DL, Rana S, Byrne SN. The suppressive effects of ultraviolet radiation on immunity in the skin and internal organs: implications for autoimmunity. J Dermatol Sci 2012; 66:176-82; http://dx.doi.org/10.1016/j.jdermsci.2011.12.009; PMID:22277701 10. Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol 2012; 132:1497500; http://dx.doi.org/10.1038/jid.2011.459; PMID:22297641
www.landesbioscience.com OncoImmunology
e27562-3
OncoImmunology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/koni20
AMD3100 protects from UV-induced skin cancer abc
Scott N Byrne
& Seri NE Sarchio
abcd
a
Cellular Photoimmunology Group; Discipline of Infectious Diseases and Immunology; Sydney Medical School; University of Sydney; Sydney, NSW Australia b
Department of Dermatology; Royal Prince Alfred Hospital; Camperdown, NSW Australia
c
Discipline of Dermatology at The Bosch Institute; Sydney Medical School; University of Sydney; Sydney, NSW Australia d
Faculty of Medicine and Health Sciences; Universiti Putra Malaysia; Malaysia Published online: 03 Jan 2014.
Click for updates To cite this article: Scott N Byrne & Seri NE Sarchio (2014) AMD3100 protects from UV-induced skin cancer, OncoImmunology, 3:2, e27562, DOI: 10.4161/onci.27562 To link to this article: http://dx.doi.org/10.4161/onci.27562
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor & Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/terms-and-conditions It is essential that you check the license status of any given Open and Open Select article to confirm conditions of access and use.
Author’s View
Paper Type
OncoImmunology 3, e27562; January 2014; © 2014 Landes Bioscience
AMD3100 protects from UV-induced skin cancer Scott N Byrne1,2,3,* and Seri NE Sarchio1,2,3,4 2
1 Cellular Photoimmunology Group; Discipline of Infectious Diseases and Immunology; Sydney Medical School; University of Sydney; Sydney, NSW Australia; Department of Dermatology; Royal Prince Alfred Hospital; Camperdown, NSW Australia; 3Discipline of Dermatology at The Bosch Institute; Sydney Medical School; University of Sydney; Sydney, NSW Australia; 4Faculty of Medicine and Health Sciences; Universiti Putra Malaysia; Malaysia
Downloaded by [Georgian Court University] at 03:04 01 February 2015
Keywords: chemokines, mast cells, skin cancer, immunosuppression, sunlight, ultraviolet radiation
Sunlight causes skin cancer by directly damaging DNA as well as by suppressing antitumor immune responses. A major mechanism whereby sunlight exerts immunosuppressive effects is by modulating the migration of chemokine (C-X-C motif) receptor 4 (CXCR4)-expressing dermal mast cells into and away from the skin. We have demonstrated the importance of this by showing that the systemic administration of the CXCR4 antagonist AMD3100 prevents sunlightinduced immunosuppression as well as the consequent carcinogenic response. Our results highlight the therapeutic potential of antagonizing CXCR4 signaling, especially in individuals who are at high risk of developing skin cancer.
Skin cancer is a growing clinical and economic problem that is primarily caused by the excessive exposure to the ultraviolet (UV) component of sunlight. In patients with severe sun damage as well as in solid organ transplant recipients (which are under immunosuppressive regimens), UV-induced squamous cell carcinoma (SCCs) is particularly aggressive and is associated with an extremely poor prognosis. Indeed, the SCCs that develop in these patients are not only more numerous than those arising in immunocompetent individuals, but also more likely to disseminate to distant organs. The successful prevention and treatment of these aggressive skin cancers require equally aggressive prevention strategies and therapeutic interventions. In turn, this requires a thorough understanding of the cellular and molecular mechanisms by which UV promotes the development of cutaneous malignancies. In addition to damaging the DNA of our skin, UV also suppresses antitumor immune responses.1 As both these events contribute to skin carcinogenesis, inhibiting either of them could reduce the incidence of skin cancer, particularly among high-risk individuals. The cellular and molecular events triggered by UV exposure converge on the activation of regulatory cells that suppress
inflammation and adaptive immune responses.1 A critical player in this process is the dermal mast cell. While traditionally associated with atopic reactions, mast cells release anti-inflammatory cytokines that enable them to perform important immunoregulatory and anti-inflammatory functions. Indeed, the production of interleukin (IL)-10 by mast cells is required to prevent an excessive cutaneous inflammation in response to UV exposuure.2 As a matter of fact, UV rays do not exert immunosuppressive effects in mast cell-deficient Wf /Wf 3 or KitWSh/W-Sh mice,4 whereas the re-engraftment of mutant mice with wild-type bone marrow-derived mast cells restores the ability of UV to suppress adaptive immunity3,4. We provided mechanistic insights into this process by demonstrating that dermal mast cells activated by UV rays migrate along a chemokine (C-X-C motif) ligand 12 (CXCL12) gradient that attracts them to nodal lymphocytes in a chemokine (C-X-C motif) receptor 4 (CXCR4)-dependent manner. This cellular rendezvous is a critical event because pharmacologically blocking the trafficking of mast cells to the lymph nodes by means of CXCR4 antagonist AMD3100 blocked the immunosuppressive effects of UV irradiation.4
AMD3100 (Plerixafor, trade name Mozobil®) has recently been approved for mobilizing hematopoietic stem cells in hematological cancer patients prior to autologous transplantation. AMD3100 has also been shown to efficiently inhibit the growth of murine ovarian cancer5 as well as the metastatic dissemination of murine melanoma.6 The ability of AMD3100 to block the migration of mast cells has been linked to its capacity to suppress the growth of murine pancreatic ductal adenocarcinoma.7 Considering the central role that the migration of mast cells as induced by UV rays and the consequent immunosuppression play in skin carcinogenesis, we hypothesized that pharmacologically antagonizing CXCR4 with AMD3100 would also prevent UV-induced skin cancer. Indeed, we have recently demonstrated that this novel CXCR4 antagonist significantly protects mice from the development of sunlight-induced SCCs.8 The ability of AMD3100 to protect mice from chronic UV exposure-induced immunosuppression and carcinogenesis was associated with the inhibition of mast cell trafficking to the skin, the developing tumor and tumor-draining lymph nodes (Fig. 1). Orally supplied AMD3100 failed to affect peripheral
*Correspondence to: Scott Byrne; Email: [email protected] Submitted: 12/12/2013; Accepted: 12/17/2013; Published Online: 01/03/2014 Citation: Byrne SN, Sarchio SN. AMD3100 protects from UV-induced skin cancer. OncoImmunology 2013; 2:e27562; http://dx.doi.org/10.4161/onci.27562
www.landesbioscience.com OncoImmunology
e27562-1
Downloaded by [Georgian Court University] at 03:04 01 February 2015
Figure 1. Systemic treatment with the CXCR4-antagonist AMD3100 significantly protects from sunlight-induced skin cancer by modulating mast cell migration. The exposure of mice to 30 wk of sun-simulating UV (UVA + UVB) light resulted in the development of histopathologically confirmed squamous cell carcinomas (SCCs) associated with elevated levels of chemokine (C-X-C motif) receptor 4 (CXCR4). This was associated with a significant accumulation of mast cells not just into the irradiated dermis, but also into neoplastic lesions and tumor-draining lymph nodes. Such an alteration of the migratory pattern of mast cells did not occur in mice continually supplied with AMD3100 in the drinking water. Moreover, AMD3100-receiving mice were protected from the immunosuppressive effects of UV light and developed very few SCCs.
blood leukocytes, as well as any of the other CXCR4-expressing cells we investigated, including Ly6a + endothelial progenitor cells, FOXP3 + regulatory T cells and myofibroblasts expressing α-smooth muscle actin. Our findings have prominent clinical and societal implications. Indeed, although minimizing sun exposure is a useful strategy to reduce the incidence of skin cancer, this public health approach has failed to make a substantial dint in statistics. Perhaps, this is because we do not know the extent to which sun exposure would have to be decreased for the
e27562-2
incidence of skin cancers to decrease. Genetic mutations and immunosuppression are both caused by less than half of the sunburning dose of sunlight,9 but the dose that promotes skin carcinogenesis in humans is unknown. The healthpromoting effects of sunlight such as vitamin D production coupled to occupational and recreational activities might make it difficult to reduce cumulative sun exposure below a level that would substantially reduce the incidence of skin cancer, even with the use of sunscreens. Compelling evidence indicating that pharmacological strategies to prevent UV
OncoImmunology
exposure-induced immunosuppression can protect humans from skin cancer has already been provided.10 Our data demonstrating that AMD3100 can prevent primary UV-induced skin cancers by selectively interfering with the ability of UV rays to modulate mast cell trafficking and consequent immunosuppression8 highlight the chemopreventive (and perhaps therapeutic) potential of antagonizing the CXCL12/CXCR4 signaling axis. Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Volume 3
References
Downloaded by [Georgian Court University] at 03:04 01 February 2015
1.
Ullrich SE, Byrne SN. The immunologic revolution: photoimmunology. J Invest Dermatol 2012; 132:896905; http://dx.doi.org/10.1038/jid.2011.405; PMID:22170491 2. Grimbaldeston MA, Nakae S, Kalesnikoff J, Tsai M, Galli SJ. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 2007; 8:1095-104; http://dx.doi.org/10.1038/ni1503; PMID:17767162 3. Hart PH, Grimbaldeston MA, Swift GJ, Jaksic A, Noonan FP, Finlay-Jones JJ. Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice. J Exp Med 1998; 187:2045-53; http://dx.doi. org/10.1084/jem.187.12.2045; PMID:9625764 4. Byrne SN, Limón-Flores AY, Ullrich SE. Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression. J Immunol 2008; 180:4648-55; PMID:18354188
5. Righi E, Kashiwagi S, Yuan J, Santosuosso M, Leblanc P, Ingraham R, Forbes B, Edelblute B, Collette B, Xing D, et al. CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer. Cancer Res 2011; 71:5522-34; http:// d x.doi.org /10.1158 / 0008 -5472.C A N-10 -3143 ; PMID:21742774 6. D’Alterio C, Barbieri A, Portella L, Palma G, Polimeno M, Riccio A, Ieranò C, Franco R, Scognamiglio G, Bryce J, et al. Inhibition of stromal CXCR4 impairs development of lung metastases. Cancer Immunol Immunother 2012; 61:1713-20; http://dx.doi. org/10.1007/s00262-012-1223-7; PMID:22399057 7. Ma Y, Hwang RF, Logsdon CD, Ullrich SE. Dynamic mast cell-stromal cell interactions promote growth of pancreatic cancer. Cancer Res 2013; 73:3927-37; http://dx.doi.org/10.1158/0008-5472.CA N-124479; PMID:23633481
8. Sarchio SNE, Scolyer RA, Beaugie C, McDonald D, Marsh-Wakefield F, Halliday GM, Byrne SN. Pharmacologically antagonizing the CXCR4CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer. J Invest Dermatol 2014; 134:1091-100; http://dx.doi.org/10.1038/ jid.2013.424; PMID:24226205 9. Halliday GM, Damian DL, Rana S, Byrne SN. The suppressive effects of ultraviolet radiation on immunity in the skin and internal organs: implications for autoimmunity. J Dermatol Sci 2012; 66:176-82; http://dx.doi.org/10.1016/j.jdermsci.2011.12.009; PMID:22277701 10. Surjana D, Halliday GM, Martin AJ, Moloney FJ, Damian DL. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol 2012; 132:1497500; http://dx.doi.org/10.1038/jid.2011.459; PMID:22297641
www.landesbioscience.com OncoImmunology
e27562-3
