Host response to cancer therapy

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The host response to cancer therapy is defined as a physiological response of the non-malignant cells of the body (also known as host cells) to a specific cancer therapy. The response is therapy-specific, occurring independently of cancer type or stage.

Background[edit]

All cancer treatment modalities (e.g., chemotherapy, targeted drugs, radiation and surgery) trigger systemic and local effects in the treated subject (i.e., the host). These include a rapid elevation in the levels of circulating cytokines, chemokines, growth factors and enzymes accompanied by acute mobilization and tumor homing of bone-marrow derived cells. These therapy-induced effects have the potential to facilitate tumor growth and spread, counteracting the beneficial effects of therapy. Thus, the host response to cancer therapy creates a paradoxical situation in which the desired therapeutic effect of treatment is reduced by its side effect on host cells. The balance between these two opposing activities determines the overall efficacy and outcome of treatment. [1][2][3][4][5]

Host response to different treatment modalities for cancer[edit]

Host response to chemotherapy[edit]

Chemotherapies, including alkylating agents, microtubule inhibitors, antimetabolites and antibiotics, represent a major systemic therapeutic modality for many cancers. These agents induce death in rapidly dividing cells thus targeting tumor cells, but at the same time damaging healthy tissue. Consequently, non-malignant host cells activate wound healing and inflammatory mechanisms to repair chemotherapy-induced damage. These repair mechanisms have the potential to exacerbate tumor promoting processes such as angiogenesis and metastasis.[1][2][6] In mouse tumor models, different chemotherapy types induce a rapid mobilization of circulating endothelial progenitor cells that home to the tumor site where they promote angiogenesis.[7] In addition, a variety of immune cell types, such as myeloid progenitors[8] [9]  and macrophages[10], are recruited to the tumor site in a chemotherapy-dependent manner, an effect that enhances metastasis.

Host response to radiation therapy[edit]

Radiotherapy is a well-established treatment modality for several cancer types. However, relapses after radiotherapy are often more aggressive and associated with poor prognosis. Cumulative evidence shows that the host response to radiotherapy is a contributing factor to this effect. Tumors implanted in pre-irradiated tissue grow with slower kinetics, however, paradoxically exhibit enhanced invasive and metastatic properties, a phenomenon known as the “tumor bed effect”.[11][12] This enhanced aggressiveness is attributed to radiation-induced modifications of the tumor microenvironment, including enhanced angiogenesis[13] and recruitment of pro-metastatic bone marrow cells[14][15][16] and macrophages[17][18][19][20]

Host response to anti-angiogenic drugs[edit]

Anti-angiogenic drugs (or angiogenesis inhibitors) target the blood vessels required for tumor survival. The rationale behind this strategy is to starve the tumor of oxygen and nutrients, limiting its ability to grow. However, tumor hypoxia that ensues activates a range of compensatory mechanisms that sustain vascularization, leading to resistance to the anti-angiogenic drug.[21][22] Many of these compensatory mechanisms involve host cells. For example, treating tumor-bearing mice with vascular-disrupting agents (that specifically target tumor-associated vessels) triggers an acute mobilization of circulating endothelial progenitor cells that home to tumor margins where they facilitate revascularization.[23] In addition, various types of pro-angiogenic bone marrow-derived cells such as myeloid-derived suppressor cells,[24][25][26] tumor-associated macrophages,[27] and TIE2-expressing monocytes[28] contribute to therapy resistance. In mouse tumor models, anti-angiogenic therapy causes an elevation in tumor-promoting cytokines and growth factors that in turn augment the invasive and metastatic potential of tumors.[29][30][31]

Host response to surgery[edit]

Surgical resection of a tumor is one of the primary treatment modalities for cancer and can be curative especially for patients with early disease. However, there is evidence that tumor resection generates a permissive environment for tumor growth, in part, via host-mediated processes. As part of the wound healing process, surgical tissue trauma is rapidly followed by a cascade of inflammatory processes.[1][32] Many of the growth factors, cytokines, extracellular matrix-modifying enzymes, and immune cells released during this process may also promote proliferation of residual tumor cells, angiogenesis and metastasis. For example, lungs are more prone to metastatic seeding after a surgical incision in the abdominal region of mice. This effect is due to increased expression and activity of lysyl oxidase (LOX), an extracellular matrix remodeling enzyme produced at the hypoxic surgical site.[33] In clinical settings, elevated levels of circulating endothelial progenitor cells, bone marrow-derived cells as well as circulating factors with known roles in angiogenesis and tumor progression have been reported in response to major surgery in comparison to minimal surgery.[34][35][36]

Clinical implications[edit]

Characterizing the host response to cancer therapy in patients has clinical implications especially in the field of personalized medicine (also known as precision medicine) and biomarker discovery. Experimental studies have shown that combining conventional cancer therapies with agents that selectively block therapy-induced factors improves treatment efficacies.[1]

References[edit]

  1. ^ a b c d Shaked, Yuval (26 April 2016). "Balancing efficacy of and host immune responses to cancer therapy: the yin and yang effects". Nature Reviews Clinical Oncology. 13 (10): 611–626. doi:10.1038/nrclinonc.2016.57. PMID 27118493.
  2. ^ a b Daenen, L G M; Houthuijzen, J M; Cirkel, G A; Roodhart, J M L; Shaked, Y; Voest, E E (25 March 2013). "Treatment-induced host-mediated mechanisms reducing the efficacy of antitumor therapies". Oncogene. 33 (11): 1341–1347. doi:10.1038/onc.2013.94. PMID 23524584.
  3. ^ Ebos, J. M. L. (30 July 2015). "Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis". Cancer Research. 75 (17): 3427–3435. doi:10.1158/0008-5472.CAN-15-0308. PMID 26229121.
  4. ^ Katz, Ofrat Beyar; Shaked, Yuval (March 2015). "Host effects contributing to cancer therapy resistance". Drug Resistance Updates. 19: 33–42. doi:10.1016/j.drup.2014.12.002. PMID 25575621.
  5. ^ Voloshin, Tali; Voest, Emile E.; Shaked, Yuval (July 2013). "The host immunological response to cancer therapy: An emerging concept in tumor biology". Experimental Cell Research. 319 (11): 1687–1695. doi:10.1016/j.yexcr.2013.03.007. PMID 23518388.
  6. ^ Karagiannis, G. S.; Condeelis, J. S.; Oktay, M. H. (2018). "Chemotherapy-induced metastasis: mechanisms and translational opportunities". Clinical & Experimental Metastasis. 35 (4): 269–284. doi:10.1007/s10585-017-9870-x. ISSN 0262-0898. PMC 6035114. PMID 29307118.
  7. ^ Shaked, Y; Henke, E; Roodhart, J. M.L.; Mancuso, P; Langenberg, M. H.G.; Colleoni, M; Daenen, L. G.; Man, S; Xu, P (2008). "Rapid Chemotherapy-Induced Acute Endothelial Progenitor Cell Mobilization: Implications for Antiangiogenic Drugs as Chemosensitizing Agents". Cancer Cell. 14 (3): 263–273. doi:10.1016/j.ccr.2008.08.001. PMC 2565587. PMID 18772115.
  8. ^ Chang, Y. S; Jalgaonkar, S. P.; Middleton, J. D.; Hai, T (2017). "Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis". Proceedings of the National Academy of Sciences. 114 (34): E7159–E7168. doi:10.1073/pnas.1700455114. ISSN 0027-8424. PMC 5576783. PMID 28784776.
  9. ^ Gingis-Velitski, S.; Loven, D.; Benayoun, L.; Munster, M.; Bril, R.; Voloshin, T.; Alishekevitz, D.; Bertolini, F.; Shaked, Y. (2011). "Host Response to Short-term, Single-Agent Chemotherapy Induces Matrix Metalloproteinase-9 Expression and Accelerates Metastasis in Mice". Cancer Research. 71 (22): 6986–6996. doi:10.1158/0008-5472.CAN-11-0629. ISSN 0008-5472. PMID 21978934.
  10. ^ Karagiannis, G. S.; Pastoriza, J. M.; Wang, Y; Harney, A. S.; Entenberg, D; Pignatelli, J; Sharma, V. P.; Xue, E. A.; Cheng, E (2017). "Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism". Science Translational Medicine. 9 (397): eaan0026. doi:10.1126/scitranslmed.aan0026. ISSN 1946-6234. PMC 5592784. PMID 28679654.
  11. ^ Arnold, K. M; Flynn, N. J; Raben, A; Romak, L; Yu, Y; Dicker, A. P; Mourtada, F; Sims-Mourtada, J (2018). "The Impact of Radiation on the Tumor Microenvironment: Effect of Dose and Fractionation Schedules". Cancer Growth and Metastasis. 11: 117906441876163. doi:10.1177/1179064418761639. ISSN 1179-0644. PMC 5846913. PMID 29551910.
  12. ^ Kuonen, F.; Secondini, C.; Ruegg, C. (2012). "Molecular Pathways: Emerging Pathways Mediating Growth, Invasion, and Metastasis of Tumors Progressing in an Irradiated Microenvironment". Clinical Cancer Research. 18 (19): 5196–5202. doi:10.1158/1078-0432.CCR-11-1758. ISSN 1078-0432. PMID 22730447.
  13. ^ Sofia Vala, I; Martins, L. R.; Imaizumi, N; Nunes, R. J.; Rino, J; Kuonen, F; Carvalho, L. M.; Rüegg, C; Grillo, I. M (2010). Gartel, Andrei L. (ed.). "Low Doses of Ionizing Radiation Promote Tumor Growth and Metastasis by Enhancing Angiogenesis". PLoS ONE. 5 (6): e11222. Bibcode:2010PLoSO...511222S. doi:10.1371/journal.pone.0011222. ISSN 1932-6203. PMC 2888592. PMID 20574535.
  14. ^ Ahn, G. O; Brown, J. M (2008). "Matrix Metalloproteinase-9 Is Required for Tumor Vasculogenesis but Not for Angiogenesis: Role of Bone Marrow-Derived Myelomonocytic Cells". Cancer Cell. 13 (3): 193–205. doi:10.1016/j.ccr.2007.11.032. PMC 2967441. PMID 18328424.
  15. ^ Kioi, M; Vogel, H; Schultz, G; Hoffman, R. M.; Harsh, G. R.; Brown, J. M (2010). "Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice". Journal of Clinical Investigation. 120 (3): 694–705. doi:10.1172/JCI40283. ISSN 0021-9738. PMC 2827954. PMID 20179352.
  16. ^ Kuonen, F.; Laurent, J.; Secondini, C.; Lorusso, G.; Stehle, J.-C.; Rausch, T.; Faes-van't Hull, E.; Bieler, G.; Alghisi, G.-C. (2012). "Inhibition of the Kit Ligand/c-Kit Axis Attenuates Metastasis in a Mouse Model Mimicking Local Breast Cancer Relapse after Radiotherapy". Clinical Cancer Research. 18 (16): 4365–4374. doi:10.1158/1078-0432.CCR-11-3028. ISSN 1078-0432. PMID 22711708.
  17. ^ Timaner, M; Bril, R; Kaidar-Person, O; Rachman-Tzemah, C; Alishekevitz, D; Kotsofruk, R; Miller, V; Nevelsky, A; Daniel, S (2015). "Dequalinium blocks macrophage-induced metastasis following local radiation". Oncotarget. 6 (29): 27537–54. doi:10.18632/oncotarget.4826. ISSN 1949-2553. PMC 4695007. PMID 26348470.
  18. ^ Chiang, Chi-Shiun; Fu, Sheng Yung; Wang, Shu-Chi; Yu, Ching-Fang; Chen, Fang-Hsin; Lin, Chi-Min; Hong, Ji-Hong (2012). "Irradiation Promotes an M2 Macrophage Phenotype in Tumor Hypoxia". Frontiers in Oncology. 2: 89. doi:10.3389/fonc.2012.00089. ISSN 2234-943X. PMC 3412458. PMID 22888475.
  19. ^ Okubo, Makiko; Kioi, Mitomu; Nakashima, Hideyuki; Sugiura, Kei; Mitsudo, Kenji; Aoki, Ichiro; Taniguchi, Hideki; Tohnai, Iwai (2016). "M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation". Scientific Reports. 6 (1): 27548. Bibcode:2016NatSR...627548O. doi:10.1038/srep27548. ISSN 2045-2322. PMC 4897643. PMID 27271009.
  20. ^ Seifert, L; Werba, G; Tiwari, S; Giao Ly, N. N; Nguy, S; Alothman, S; Alqunaibit, D; Avanzi, A; Daley, D (2016). "Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice". Gastroenterology. 150 (7): 1659–1672.e5. doi:10.1053/j.gastro.2016.02.070. PMC 4909514. PMID 26946344.
  21. ^ Ebos, J. M. L.; Kerbel, R. S. (2011). "Antiangiogenic therapy: impact on invasion, disease progression and metastasis". Nature Reviews Clinical Oncology. 8 (4): 210–221. doi:10.1038/nrclinonc.2011.21. ISSN 1759-4774. PMC 4540336. PMID 21364524.
  22. ^ Ebos, J. M. L.; Lee, C. R.; Kerbel, R. S. (2009). "Tumor and Host-Mediated Pathways of Resistance and Disease Progression in Response to Antiangiogenic Therapy". Clinical Cancer Research. 15 (16): 5020–5025. doi:10.1158/1078-0432.CCR-09-0095. ISSN 1078-0432. PMC 2743513. PMID 19671869.
  23. ^ Shaked, Y. (22 September 2006). "Therapy-Induced Acute Recruitment of Circulating Endothelial Progenitor Cells to Tumors". Science. 313 (5794): 1785–1787. Bibcode:2006Sci...313.1785S. doi:10.1126/science.1127592. PMID 16990548.
  24. ^ Shojaei, Farbod; Wu, Xiumin; Malik, Ajay K; Zhong, Cuiling; Baldwin, Megan E; Schanz, Stefanie; Fuh, Germaine; Gerber, Hans-Peter; Ferrara, Napoleone (29 July 2007). "Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells". Nature Biotechnology. 25 (8): 911–920. doi:10.1038/nbt1323. PMID 17664940.
  25. ^ Shojaei, F.; Wu, X.; Qu, X.; Kowanetz, M.; Yu, L.; Tan, M.; Meng, Y. G.; Ferrara, N. (3 April 2009). "G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models". Proceedings of the National Academy of Sciences. 106 (16): 6742–6747. Bibcode:2009PNAS..106.6742S. doi:10.1073/pnas.0902280106. PMC 2665197. PMID 19346489.
  26. ^ Shojaei, Farbod; Wu, Xiumin; Zhong, Cuiling; Yu, Lanlan; Liang, Xiao-Huan; Yao, Jenny; Blanchard, Dominique; Bais, Carlos; Peale, Franklin V.; van Bruggen, Nicholas; Ho, Calvin; Ross, Jed; Tan, Martha; Carano, Richard A. D.; Meng, Y. Gloria; Ferrara, Napoleone (December 2007). "Bv8 regulates myeloid-cell-dependent tumour angiogenesis". Nature. 450 (7171): 825–831. Bibcode:2007Natur.450..825S. doi:10.1038/nature06348. PMID 18064003.
  27. ^ Zhang, W.; Zhu, X.-D.; Sun, H.-C.; Xiong, Y.-Q.; Zhuang, P.-Y.; Xu, H.-X.; Kong, L.-Q.; Wang, L.; Wu, W.-Z.; Tang, Z.-Y. (22 June 2010). "Depletion of Tumor-Associated Macrophages Enhances the Effect of Sorafenib in Metastatic Liver Cancer Models by Antimetastatic and Antiangiogenic Effects". Clinical Cancer Research. 16 (13): 3420–3430. doi:10.1158/1078-0432.CCR-09-2904. PMID 20570927.
  28. ^ Lewis, C. E.; De Palma, M.; Naldini, L. (2007). "Tie2-Expressing Monocytes and Tumor Angiogenesis: Regulation by Hypoxia and Angiopoietin-2". Cancer Research. 67 (18): 8429–8432. doi:10.1158/0008-5472.CAN-07-1684. ISSN 0008-5472. PMID 17875679.
  29. ^ Ebos, J.M.L.; Lee, C. R.; Cruz-Munoz, W; Bjarnason, G. A.; Christensen, J. G.; Kerbel, R. S. (2009). "Accelerated Metastasis after Short-Term Treatment with a Potent Inhibitor of Tumor Angiogenesis". Cancer Cell. 15 (3): 232–239. doi:10.1016/j.ccr.2009.01.021. PMC 4540346. PMID 19249681.
  30. ^ Pàez-Ribes, M; Allen, E; Hudock, J; Takeda, T; Okuyama, H; Viñals, F; Inoue, M; Bergers, G; Hanahan, D (2009). "Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis". Cancer Cell. 15 (3): 220–231. doi:10.1016/j.ccr.2009.01.027. PMC 2874829. PMID 19249680.
  31. ^ Ebos, J. M. L.; Lee, C. R.; Christensen, J. G.; Mutsaers, A. J.; Kerbel, R. S. (2007). "Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy". Proceedings of the National Academy of Sciences. 104 (43): 17069–17074. Bibcode:2007PNAS..10417069E. doi:10.1073/pnas.0708148104. ISSN 0027-8424. PMC 2040401. PMID 17942672.
  32. ^ Ceelen, W; Pattyn, P; Mareel, M (2014). "Surgery, wound healing, and metastasis: Recent insights and clinical implications". Critical Reviews in Oncology/Hematology. 89 (1): 16–26. doi:10.1016/j.critrevonc.2013.07.008. PMID 23958676.
  33. ^ Rachman-Tzemah, C; Zaffryar-Eilot, S; Grossman, M; Ribero, D; Timaner, M; Mäki, J. M.; Myllyharju, J; Bertolini, F; Hershkovitz, D (2017). "Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases". Cell Reports. 19 (4): 774–784. doi:10.1016/j.celrep.2017.04.005. PMC 5413586. PMID 28445728.
  34. ^ Bono, Anna; Bianchi, Paolo; Locatelli, Andrea; Calleri, Angelica; Quarna, Jessica; Antoniott, Pierluigi; Rabascio, Cristina; Mancuso, Patrizia; Andreoni, Bruno; Bertolini, Francesco (27 October 2014). "Angiogenic cells, macroparticles and RNA transcripts in laparoscopic vs open surgery for colorectal cancer". Cancer Biology & Therapy. 10 (7): 682–685. doi:10.4161/cbt.10.7.12898. PMID 20676027.
  35. ^ Curigliano, G.; Petit, J. Y.; Bertolini, F.; Colleoni, M.; Peruzzotti, G.; de Braud, F.; Gandini, S.; Giraldo, A.; Martella, S. (2005). "Systemic Effects of Surgery: Quantitative Analysis of Circulating Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) and Transforming Growth Factor Beta (TGF-β) in Patients with Breast Cancer Who Underwent Limited or Extended Surgery". Breast Cancer Research and Treatment. 93 (1): 35–40. doi:10.1007/s10549-005-3381-1. ISSN 0167-6806. PMID 16184456.
  36. ^ Langenberg, Marlies H.G.; Nijkamp, Maarten W.; Roodhart, Jeanine M.L.; Snoeren, Nikol; Tang, Terence; Shaked, Yuval; Hillegersberg, Richard van; Witteveen, Petronella O.; Vermaat, Joost S.P.; Kranenburg, Onno; Kerbel, Robert S.; Medema, Rene H.; Borel Rinkes, Inne H.M.; Voest, Emile E. (27 October 2014). "Liver surgery induces an immediate mobilization of progenitor cells in liver cancer patients: A potential role for G-CSF". Cancer Biology & Therapy. 9 (9): 743–748. doi:10.4161/cbt.9.9.11551. PMID 20215863.