АЛЛЕРГИЯ ИЛИ ОНКОЛОГИЯ?
Аннотация
И аллергические, и онкологические заболевания представляют собой две глобальные проблемы современной медицины, далекие от своего решения. Обе патологии являются иммуноопосредованными, но в случае аллергии имеет место гиперчувствительность вследствие срыва иммунной толерантности, а в случае онкологии заболевание развивается именно из-за иммунной недостаточности, связанной с избыточной толерантностью. Ключевым фактором роста злокачественной опухоли является формирование максимально «дружественной» среды со стороны ее микроокружения. Различные компоненты иммунитета, теоретически, должны эффективно распознавать и уничтожать клетки опухоли еще на начальных этапах ее развития, до образования клинически значимого опухолевого роста. Однако клинические исследования говорят об обратном. Различные компоненты иммунной системы (опухоль-ассоциированные макрофаги, цитокины — факторы роста, супрессорные клетки миелоидного происхождения) участвуют в патогенезе опухолевого роста, не противодействуя, а способствуя развитию новообразования, его инвазии и метастазированию. И поэтому одной из основных целей в области лечения онкологических заболеваний является разработка вмешательств, которые могут нарушить иммунологическую толерантность и остановить прогрессирование рака. Многочисленные эпидемиологические исследования предполагают обратную ассоциацию между аллергическими заболеваниями и развитием злокачественных новообразований. Немало также доказательств концепции способности клеток иммунной системы и IgE разрушать опухолевые клетки. Проводятся многочисленные исследования in vitro, которые «нацеливают» данный класс антител на соответствующие опухолевые антигены. Было продемонстрировано, что антитела класса IgE специфичны для сверхэкспрессированной опухоли, они превосходили любой другой класс иммуноглобулинов в отношении антителозависимой клеточной цитотоксичности (ADCC — antibody-dependent cell-mediated cytotoxicity) и фагоцитоза (ADCP — antibody-dependent cell-mediated phagocytosis). И поэтому эозинофилы, тучные клетки и макрофаги в совокупности с IgE могут стать мощными противоопухолевыми эффекторами. Специфичный к опухолевым антигенам IgE вызывает эозинофил-опосредованную гибель опухолевых клеток цитотоксическими механизмами. Характер влияния тучных клеток на опухоль определяется комплексом факторов. Установлено, что в зависимости от своей локализации по отношению к опухоли тучные клетки могут демонстрировать разнонаправленные эффекты. Неоднозначные свойства клеток иммунной системы, синтезируемых ими медиаторов и различных классов иммуноглобулинов привлекают внимание исследователей всего мира. Было установлено, что между наличием у пациента аллергии и риском развития некоторых видов рака (глиома, рак поджелудочной железы и детский лейкоз) прослеживается обратная зависимость. Данные проспективных исследований подтвердили также негативную ассоциацию аллергии с колоректальным раком.
Литература
Angelin A., Gil-de-Gomez L., Dahiya S. et al. Foxp3 reprograms T Cell metabolism to function in low-glucose, high-lactate environments. Cell Metab. 2017; 25: 1282–93.
Asai A., Nakamura K., Kobayashi M. et al. CCL1 released from M2b macrophages is essentially required for the maintenance of their properties. J. Leukoc. Biol. 2012; 92: 859–67.
Bashford-Rogers R.J., Nicolaou K.A., Bartram J. et al. Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse. Leukemia. 2016; 30: 2312–21.
Beyer M., Mallmann M.R., Xue J. et al. High-resolution transcriptome of human macrophages. PLoS One. 2012; 7: e45466.
Bluth M.H. IgE and chemotherapy. Cancer Immunol Immunother. 2012; 61: 1585–90.
Cahoon E.K., Inskip P.D., Gridley G., Brenner A.V. Immunerelated conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans. Br. J. Cancer. 2014; 110: 1825–33.
Chaudhary B., Elkord E. Regulatory T-cells in the tumor microenvironment and cancer progression: role and therapeutic targeting. Vaccines. 2016: 4: e28.
Chen X., Churchill M.J., Nagar K.K. et al. IL-17 producing mast cells promote the expansion of myeloid-derived suppressor cells in a mouse allergy model of colorectal cancer. Oncotarget. 2015; 6: 32966–79.
Cipolat S., Hoste E., Natsuga K. et al. Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility. eLife. 2014; 3: e01888.
Cortez V.S., Robinette M.L., Colonna M. Innate lymphoid cells: new insights into function and development. Curr. Opin. Immunol. 2015; 32: 71–7.
Dalton D.K., Noelle R.J. The roles of mast cells in anticancer immunity. Cancer Immunol. Immunother. 2012; 61: 1511–20.
Daniels T.R., Leuchter R.K., Quintero R. et al. Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells. Cancer Immunol Immunother. 2012; 61: 991–1003.
Demehri S., Cunningham T.J., Manivasagam S. et al. Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J. Clin. Invest. 2016; 126: 1458–70.
De Vries V.C., Wasiuk A., Bennett K.A. et al. Mast cell degranulation breaks peripheral tolerance. Am. J. Transplant. 2009; 9: 2270–80.
Erreni M., Mantovani A., Allavena P. Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenviron. 2011; 4: 141–54.
Fu S.L., Pierre J., Smith-Norowitz T.A. et al. Immunoglobulin E antibodies from pancreatic cancer patients mediate antibodydependent cell-mediated cytotoxicity against pancreatic cancer cells. Clin. Exp. Immunol. 2008; 153: 401–9.
Gatault S., Legrand F., Delbeke M. et al. Involvement of eosinophils in the antitumor response. Cancer Immunol. Immunother. 2012; 61: 1527–34.
Gatault S., Delbeke M., Driss V. et al. IL-18 is involved in eosinophil-mediated tumoricidal activity against a colon carcinoma cell line by upregulating LFA-1 and ICAM-1. J. Immunol. 2015; 195: 2483–92.
Gould H.J., Takhar P., Harries H.E. et al. Germinal-centre reactions in allergic inflammation. Trends in Immunology. 2006; 27: 446–52.
Gordon J.R., Ma Y., Churchman L. et al. Regulatory dendritic cells for immunotherapy in immunologic diseases. Front Immunol. 2014; 5(7): 1–19.
Groot Kormelink T., Powe D.G., Kuijpers S.A. et al. Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation. Oncotarget. 2014; 5: 3159–67.
Jacobs E.J., Gapstur S.M., Newton C.C. et al. Hay Fever and asthma as markers of atopic immune response and risk of colorectal cancer in three large cohort studies. Cancer Epidemiol. Biomarkers Prev. 2013; 22: 661–9.
Jensen-Jarolim E., Pacios L.F., Bianchini R. et al. Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy. Allergy. 2016; 71: 286–94.
Jiang L., Shen Y., Guo D. et al. EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance. Nat. Commun. 2016; 7: e13045.
Johansson A., Rudolfsson S., Hammarsten P. et al. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am. J. Pathol. 2010; 177: 1031–41.
Karagiannis S.N., Bracher M.G., Hunt J. et al. IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J. Immunol. 2007; 179: 2832–43.
Kirchberger S., Royston D.J., Boulard O. et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 2013; 210(5): 917–31.
Lechner M.G., Liebertz D.J., Epstein A.L. Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. The Journal of Immunology. 2010; 185(4): 2273–84.
Legrand F., Driss V., Delbeke M. et al. Human eosinophils exert TNF-alpha and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J. Immunol. 2010; 185(12): 7443–51.
Liu X., Jin H., Zhang G. et al. Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients. PLoS One. 2014; 9: e106834.
Lotfi R., Kaltenmeier C., Lotze M.T., Bergmann C. Until death do us part: necrosis and oxidation promote the tumor microenvironment. Transfus. Med. Hemother. 2016; 43: 120–32.
Makris K., Rizos D., Kafkas N., Haliassos A. Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine. Clin. Chem. Lab. Med. 2012; 50: 1519–32.
Matta G.M., Battaglio S., Dibello C. et al. Polyclonal immunoglobulin E levels are correlated with hemoglobin values and overall survival in patients with multiple myeloma. Clin. Cancer Res. 2007; 13: 5348–54.
Miyatani K., Saito H., Murakami Y. et al. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. Virchows Arch. 2016; 468: 549–57.
Pittoni P., Tripodo C., Piconese S. et al. Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res. 2011; 71: 5987–97.
Platzer B., Elpek K.G., Cremasco V. et al. IgE/FcεRI-mediated antigen cross-presentation by dendritic cells enhances anti-tumor immune responses. Cell Rep. 2015: e02.015.
Prizment A.E., Anderson K.E., Visvanathan K., Folsom A.R. Inverse association of eosinophil count with colorectal cancer incidence: atherosclerosis risk in communities study. Cancer Epidemiol Biomarkers Prev. 2011; 20: 1861–4.
Raker V.K., Domogalla M.P., Steinbrink K. Tolerogenic dendritic cells for regulatory T cell induction in man. Front Immunol. 2015; 6: 569.
Robainas M., Otano R., Bueno S., Ait-Oudhia S. Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy. Onco. Targets Ther. 2017; 10: 1803–7.
Rodrigues C.P., Ferreira A.C., Pinho M.P. et al. Tolerogenic IDO (+) dendritic cells are induced by PD-1-expressing mast cells. Front Immunol. 2016; 7: 9.
Roszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm. 2015; 2015: e816460.
Schatton T., Schutte U., Frank M.H. Effects of malignant melanoma initiating cells on T-cell activation. Methods Mol. Biol. 2016: 1–12.
Schlecker E., Stojanovic A., Eisen C. et al. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T-cells favoring tumor growth. J. Immunol. 2012; 189: 5602–11.
Turner M.C. Epidemiology: allergy history, IgE, and cancer. Cancer Immunol. Immunother. 2012; 61: 1493–1510.
Umansky V., Blattner C., Gebhardt C., Utikal J. CCR5 in recruitment and activation of myeloid-derived suppressor cells in melanoma. Cancer Immunol Immunother. 2017; 66: 1015–23.
Wawrzyniak M., O’Mahony L., Akdis M. Role of regulatory cells in oral tolerance. Allergy Asthma Immunol. Res. 2017; 9: 107–15.
Wen C.P., Lee J.H., Tai Y.P. et al. High serum iron is associated with increased cancer risk. Cancer Res. 2014; 74: 6589–97.
Wulaningsih W., Holmberg L., Garmo H. et al. Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival. OncoImmunology. 2016; 5: e1154250.
Yang Z., Zhang B., Li D. et al. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS One. 2010; 5: e8922.
Zaiss D.M., van Loosdregt J., Gorlani A. et al. Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor. Immunity. 2013; 38: 275–84.
REFERENCES
Angelin A., Gil-de-Gomez L., Dahiya S. et al. Foxp3 reprograms T Cell metabolism to function in low-glucose, high-lactate environments. Cell Metab. 2017; 25: 1282–93.
Asai A., Nakamura K., Kobayashi M. et al. CCL1 released from M2b macrophages is essentially required for the maintenance of their properties. J. Leukoc. Biol. 2012; 92: 859–67.
Bashford-Rogers R.J., Nicolaou K.A., Bartram J. et al. Eye on the B-ALL: B-cell receptor repertoires reveal persistence of numerous B-lymphoblastic leukemia subclones from diagnosis to relapse. Leukemia. 2016; 30: 2312–21.
Beyer M., Mallmann M.R., Xue J. et al. High-resolution transcriptome of human macrophages. PLoS One. 2012; 7: e45466.
Bluth M.H. IgE and chemotherapy. Cancer Immunol Immunother. 2012; 61: 1585–90.
Cahoon E.K., Inskip P.D., Gridley G., Brenner A.V. Immunerelated conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans. Br. J. Cancer. 2014; 110: 1825–33.
Chaudhary B., Elkord E. Regulatory T-cells in the tumor microenvironment and cancer progression: role and therapeutic targeting. Vaccines. 2016: 4: e28.
Chen X., Churchill M.J., Nagar K.K. et al. IL-17 producing mast cells promote the expansion of myeloid-derived suppressor cells in a mouse allergy model of colorectal cancer. Oncotarget. 2015; 6: 32966–79.
Cipolat S., Hoste E., Natsuga K. et al. Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility. eLife. 2014; 3: e01888.
Cortez V.S., Robinette M.L., Colonna M. Innate lymphoid cells: new insights into function and development. Curr. Opin. Immunol. 2015; 32: 71–7.
Dalton D.K., Noelle R.J. The roles of mast cells in anticancer immunity. Cancer Immunol. Immunother. 2012; 61: 1511–20.
Daniels T.R., Leuchter R.K., Quintero R. et al. Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells. Cancer Immunol Immunother. 2012; 61: 991–1003.
Demehri S., Cunningham T.J., Manivasagam S. et al. Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J. Clin. Invest. 2016; 126: 1458–70.
De Vries V.C., Wasiuk A., Bennett K.A. et al. Mast cell degranulation breaks peripheral tolerance. Am. J. Transplant. 2009; 9: 2270–80.
Erreni M., Mantovani A., Allavena P. Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenviron. 2011; 4: 141–54.
Fu S.L., Pierre J., Smith-Norowitz T.A. et al. Immunoglobulin E antibodies from pancreatic cancer patients mediate antibodydependent cell-mediated cytotoxicity against pancreatic cancer cells. Clin. Exp. Immunol. 2008; 153: 401–9.
Gatault S., Legrand F., Delbeke M. et al. Involvement of eosinophils in the antitumor response. Cancer Immunol. Immunother. 2012; 61: 1527–34.
Gatault S., Delbeke M., Driss V. et al. IL-18 is involved in eosinophil-mediated tumoricidal activity against a colon carcinoma cell line by upregulating LFA-1 and ICAM-1. J. Immunol. 2015; 195: 2483–92.
Gould H.J., Takhar P., Harries H.E. et al. Germinal-centre reactions in allergic inflammation. Trends in Immunology. 2006; 27: 446–52.
Gordon J.R., Ma Y., Churchman L. et al. Regulatory dendritic cells for immunotherapy in immunologic diseases. Front Immunol. 2014; 5(7): 1–19.
Groot Kormelink T., Powe D.G., Kuijpers S.A. et al. Immunoglobulin free light chains are biomarkers of poor prognosis in basal-like breast cancer and are potential targets in tumor-associated inflammation. Oncotarget. 2014; 5: 3159–67.
Jacobs E.J., Gapstur S.M., Newton C.C. et al. Hay Fever and asthma as markers of atopic immune response and risk of colorectal cancer in three large cohort studies. Cancer Epidemiol. Biomarkers Prev. 2013; 22: 661–9.
Jensen-Jarolim E., Pacios L.F., Bianchini R. et al. Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy. Allergy. 2016; 71: 286–94.
Jiang L., Shen Y., Guo D. et al. EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance. Nat. Commun. 2016; 7: e13045.
Johansson A., Rudolfsson S., Hammarsten P. et al. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am. J. Pathol. 2010; 177: 1031–41.
Karagiannis S.N., Bracher M.G., Hunt J. et al. IgE-antibody-dependent immunotherapy of solid tumors: cytotoxic and phagocytic mechanisms of eradication of ovarian cancer cells. J. Immunol. 2007; 179: 2832–43.
Kirchberger S., Royston D.J., Boulard O. et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 2013; 210(5): 917–31.
Lechner M.G., Liebertz D.J., Epstein A.L. Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. The Journal of Immunology. 2010; 185(4): 2273–84.
Legrand F., Driss V., Delbeke M. et al. Human eosinophils exert TNF-alpha and granzyme A-mediated tumoricidal activity toward colon carcinoma cells. J. Immunol. 2010; 185(12): 7443–51.
Liu X., Jin H., Zhang G. et al. Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients. PLoS One. 2014; 9: e106834.
Lotfi R., Kaltenmeier C., Lotze M.T., Bergmann C. Until death do us part: necrosis and oxidation promote the tumor microenvironment. Transfus. Med. Hemother. 2016; 43: 120–32.
Makris K., Rizos D., Kafkas N., Haliassos A. Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine. Clin. Chem. Lab. Med. 2012; 50: 1519–32.
Matta G.M., Battaglio S., Dibello C. et al. Polyclonal immunoglobulin E levels are correlated with hemoglobin values and overall survival in patients with multiple myeloma. Clin. Cancer Res. 2007; 13: 5348–54.
Miyatani K., Saito H., Murakami Y. et al. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. Virchows Arch. 2016; 468: 549–57.
Pittoni P., Tripodo C., Piconese S. et al. Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res. 2011; 71: 5987–97.
Platzer B., Elpek K.G., Cremasco V. et al. IgE/FcεRI-mediated antigen cross-presentation by dendritic cells enhances anti-tumor immune responses. Cell Rep. 2015: e02.015.
Prizment A.E., Anderson K.E., Visvanathan K., Folsom A.R. Inverse association of eosinophil count with colorectal cancer incidence: atherosclerosis risk in communities study. Cancer Epidemiol Biomarkers Prev. 2011; 20: 1861–4.
Raker V.K., Domogalla M.P., Steinbrink K. Tolerogenic dendritic cells for regulatory T cell induction in man. Front Immunol. 2015; 6: 569.
Robainas M., Otano R., Bueno S., Ait-Oudhia S. Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy. Onco. Targets Ther. 2017; 10: 1803–7.
Rodrigues C.P., Ferreira A.C., Pinho M.P. et al. Tolerogenic IDO (+) dendritic cells are induced by PD-1-expressing mast cells. Front Immunol. 2016; 7: 9.
Roszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm. 2015; 2015: e816460.
Schatton T., Schutte U., Frank M.H. Effects of malignant melanoma initiating cells on T-cell activation. Methods Mol. Biol. 2016: 1–12.
Schlecker E., Stojanovic A., Eisen C. et al. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T-cells favoring tumor growth. J. Immunol. 2012; 189: 5602–11.
Turner M.C. Epidemiology: allergy history, IgE, and cancer. Cancer Immunol. Immunother. 2012; 61: 1493–1510.
Umansky V., Blattner C., Gebhardt C., Utikal J. CCR5 in recruitment and activation of myeloid-derived suppressor cells in melanoma. Cancer Immunol Immunother. 2017; 66: 1015–23.
Wawrzyniak M., O’Mahony L., Akdis M. Role of regulatory cells in oral tolerance. Allergy Asthma Immunol. Res. 2017; 9: 107–15.
Wen C.P., Lee J.H., Tai Y.P. et al. High serum iron is associated with increased cancer risk. Cancer Res. 2014; 74: 6589–97.
Wulaningsih W., Holmberg L., Garmo H. et al. Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival. OncoImmunology. 2016; 5: e1154250.
Yang Z., Zhang B., Li D. et al. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS One. 2010; 5: e8922.
Zaiss D.M., van Loosdregt J., Gorlani A. et al. Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor. Immunity. 2013; 38: 275–84.
