Open Access

Tumor progression mechanisms: Insights from the central immune regulation of tissue homeostasis (Review)

  • Authors:
    • Natalya Lisovska
    • Nasrulla Shanazarov
  • View Affiliations

  • Published online on: April 5, 2019     https://doi.org/10.3892/ol.2019.10218
  • Pages: 5311-5318
  • Copyright: © Lisovska et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Knowledge of the mechanisms underlying the spread of cancer at the cellular and molecular levels is expanding rapidly. However, the central regulators governing the initiation and the rate of tumor growth remain poorly established. The fundamental principles of innate and adaptive immunity may explain how immune cells generate a specific response to tumor tissue. In the current review, the functional features of the immune system that contribute to the maintenance of normal tissue homeostasis, as well as their disruption in malignant transformations, were analyzed. Experimental and clinical studies previously demonstrated the involvement of regulatory T‑cells in the process of tumor metastasis in a tissue‑specific manner. An understanding of the cross talk between lymphoid and tumor cells may provide an insight into cancer evolution in terms of the mechanisms of T‑cell competency formation. Elucidating the mechanisms of tumor progression via central immune regulation has implications for the development of novel therapeutic agents that target immune checkpoints.

References

1 

Jiang WG and Ablin RJ: Cancer metastasis, challenges, progress and the opportunities. Front Biosci (Elite Ed). 3:391–394. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Kitamura T, Qian BZ and Pollard JW: Immune cell promotion of metastasis. Nat Rev Immunol. 15:73–86. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Smith HA and Kang YT: The metastasis-promoting roles of tumor-associated immune cells. J Mol Med (Berl). 91:411–429. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Fridman WH, Pages F, Sautes-Fridman C and Galon J: The immune contexture in human tumours: Impact on clinical outcome. Nat Rev Cancer. 12:298–306. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Zlotnic A and Yoshie O: The chemokine superfamily revisited. Immunity. 36:705–716. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Almeida FF and Belz GT: Innate lymphoid cells: Models of plasticity for immune homeostasis and rapid responsiveness in protection. Mucosal Immunol. 9:1103–1112. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Corrado C, Raimondo S, Chiesi A, Ciccia F, De Leo G and Alessandro R: Exosomes as intercellular signaling organelles involved in health and disease: Basic science and clinical applications. Int J Mol Sci. 14:5338–5366. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Wang CM, Ploia C, Anselmi F, Sarukhan A and Viola A: Adenosine triphosphate acts as a paracrine signaling molecule to reduce the motility of T cells. EMBO J. 33:1354–1364. 2014.PubMed/NCBI

9 

Fidler IJ: Lymphocytes are not only immunocytes. Biomedicine. 32:1–3. 1980.PubMed/NCBI

10 

Senovilla L, Galluzzi L, Zitvogel L and Kroemer G: Immunosurveillance as a regulator of tissue homeostasis. Trends Immunol. 34:471–481. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Hu W and Pasare C: Location, location, location: Tissue-specific regulation of immune responses. J Leukoc Biol. 94:409–421. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Shechter R, London A and Schwartz M: Orchestrated leukocyte recruitment to immune-privileged sites: Absolute barriers versus educational gates. Nat Rev Immunol. 13:206–218. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Schaerli P, Ebert L, Willimann K, Blaser A, Roos RS, Loetscher P and Moser B: A skin-selective homing mechanism for human immune surveillance T cells. J Exp Med. 199:1265–1275. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Satija R and Shalek AK: Heterogeneity in immune responses: From populations to single cells. Trends Immunol. 35:219–229. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Caramalho I, Nunes-Cabaco H, Foxall RB and Sousa AE: Regulatory T-cell development in the human thymus. Front Immunol. 6:3952015. View Article : Google Scholar : PubMed/NCBI

16 

Ge Q, Hu H, Eisen HN and Chen J: Different contributions of thymopoiesis and homeostasis-driven proliferation to the reconstitution of naive and memory T cell compartments. Proc Natl Acad Sci USA. 99:2989–2994. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Chinn IK, Blackburn CC, Manley NR and Semprowski GD: Changes in primary lymphoid organs with aging. Semin Immunol. 24:309–320. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Ucar O, Li K, Dvornicov D, Kreutz C, Timmer J, Matt S, Brenner L, Smedley S, Travis MA, Hoffman TG, et al: A thymic epithelial stem cell pool persists throughout ontogeny and is modulated by TGF-β. Cell Rep. 17:448–457. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Hsieh CS, Lee HM and Lio CW: Selection of regulatory T cells in the thymus. Nat Rev Immunol. 12:157–567. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Dobrzanski MJ: Expanding roles for CD4 T cells and their subpopulations in tumor immunity and therapy. Front Oncol. 3:632013. View Article : Google Scholar : PubMed/NCBI

21 

von Boehmer H: The thymus in immunity and in malignancy. Cancer Immunol Res. 2:592–597. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Dong J, Chen Y, Xu X, Jin R, Teng F, Yan F, Tang H, Li P, Sun X, Li Y, et al: Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus. PLoS One. 8:e563782013. View Article : Google Scholar : PubMed/NCBI

23 

Munoz MA, Biro M and Weninger W: T cell migration in intact lymph nodes in vivo. Curr Opin Cell Biol. 30:17–24. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Singh NK, Riley TP, Baker SCB, Borrman T, Weng Z and Baker BM: Emerging concepts in TCR specificity: Rationalizing and (maybe) predicting outcomes. J Immunol. 199:2203–2213. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Parrish HL, Deshpande NR, Vasic J and Kuhns MS: Functional evidence for TCR-intrinsic specificity for MHCII. Proct Natl Acad Sci USA. 113:3000–3005. 2016. View Article : Google Scholar

26 

Sethna Z, Elhanati Y, Dudgeon CS, Callan CG Jr, Levine AJ, Mora T and Walczak AM: Insights into immune system development and function from mouse T-cell repertoires. Proc Natl Acad Sci USA. 114:2253–2258. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Muller WA: How endothelial cells regulate transmigration of leukocytes in the inflammatory response. Am J Pathol. 184:886–896. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Anders HJ, Romagnani P and Mantovani A: Pathomechanisms: Homeostatic chemokines in health, tissue regeneration, and progressive diseases. Trends Mol Med. 20:154–165. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, et al: Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 16:628–634. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Farber DL, Yudanin NA and Restifo NP: Human memory T cells: Generation, compartmentalization and homeostasis. Nat Rev Immunol. 14:24–35. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Halkias J, Melichar HJ, Taylor KT and Robey EA: Tracking migration during human T cell development. Cell Mol Life Sci. 71:3101–3117. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Dominguez GA, Anderson NR and Hammer DA: The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged. Integr Biol (Camb). 7:345–355. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Mrass P, Petravic J, Davenport MP and Weninger W: Cell-autonomous and environmental contributions to the interstitial migration of T cells. Semin Immunopathol. 32:257–274. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Ruddle NH: Lymphatic vessels and tertiary lymphoid organs. J Clin Invest. 124:953–959. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Mai J, Virtue A, Shen J, Wang H and Yang XF: An evolving new paradigm: Endothelial cells-conditional innate immune cells. J Hematol Oncol. 6:612013. View Article : Google Scholar : PubMed/NCBI

36 

Smigiel KS, Srivastava S, Stolley JM and Campbell DJ: Regulatory T-cell homeostasis: Steady-state maintenance and modulation during inflammation. Immunol Rev. 259:40–59. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Feinerman O, Jentsch G, Tkach KE, Coward JW, Hathorn MM, Sneddon MW, Emonet T, Smith KA and Altan-Bonnet G: Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response. Mol Syst Biol. 6:4372010. View Article : Google Scholar : PubMed/NCBI

38 

Barbi J, Pardoll D and Pan F: Treg functional stability and its responsiveness to the microenvironment. Immunol Rev. 259:115–139. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Zhan Y, Bourges D, Dromey JA, Harrison LC and Lew AM: The origin of thymic CD4+CD25+ regulatory T cells and their co-stimulatory requirements are determined after elimination of recirculating peripheral CD4+ cells. Int Immunol. 19:455–463. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Mittelbrunn M and Sánchez-Madrid F: Intercellular communication: Diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol. 13:328–335. 2012. View Article : Google Scholar : PubMed/NCBI

41 

Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F, González MÁ, Bernad A and Sanchez-Madrid F: Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commune. 2:2822011. View Article : Google Scholar

42 

Azmi AS, Bao B and Sarkar FH: Exosomes in cancer development, metastasis, and drug resistance: A comprehensive review. Cancer Metastasis Rev. 32:623–642. 2013. View Article : Google Scholar : PubMed/NCBI

43 

Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, et al: Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 4:270662015. View Article : Google Scholar : PubMed/NCBI

44 

Green DR, Droin N and Pinkoski M: Activation-induced cell death in T cells. Immunol Rev. 193:70–81. 2003. View Article : Google Scholar : PubMed/NCBI

45 

Ventimiglia LN and Alonso MA: Biogenesis and function of T cell-derived exosomes. Front Cell Dev Biol. 4:842016. View Article : Google Scholar : PubMed/NCBI

46 

Tang Q, Jiang D, Harfuddin Z, Cheng K, Moh MC and Schwarz H: Regulation of myelopoiesis by CD137L signaling. Int Rev Immunol. 33:454–469. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Medler TR and Coussens LM: Duality of the immune response in cancer: Lessons learned from skin. J Invest Dermatol. 134:E23–E28. 2014. View Article : Google Scholar : PubMed/NCBI

48 

Savage PA, Leventhal DS and Malchow S: Shaping the repertoire of tumor-infiltrating effector and regulatory T cells. Immunol Rev. 259:245–258. 2014. View Article : Google Scholar : PubMed/NCBI

49 

Seyfried TN and Huysentruyt LC: On the origin of cancer metastasis. Crit Rev Oncog. 18:43–73. 2013. View Article : Google Scholar : PubMed/NCBI

50 

Keskinov AA and Shurin MR: Myeloid regulatory cells in tumor spreading and metastasis. Immunobiology. 220:236–242. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Kovács KA, Hegedus B, Kenessey I and Tímár J: Tumor type-specific and skin region-selective metastasis of human cancers: Another example of the ‘seed and soil’ hypothesis. Cancer Metastasis Rev. 32:493–499. 2013. View Article : Google Scholar : PubMed/NCBI

52 

Ben-Baruch A: Organ selectivity in metastasis: Regulation by chemokines and their receptors. Clin Exp Metastasis. 25:345–356. 2008. View Article : Google Scholar : PubMed/NCBI

53 

Satelli A, Mitra A, Brownlee Z, Xia X, Bellister S, Overman MJ, Kopetz S, Ellis LM, Meng QH and Li S: Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. Clin Cancer Res. 21:899–906. 2015. View Article : Google Scholar : PubMed/NCBI

54 

Dasgupta A, Lim AR and Ghajar CM: Circulating and disseminated tumor cells: Harbingers or initiators of metastasis? Mol Oncol. 11:40–61. 2017. View Article : Google Scholar : PubMed/NCBI

55 

Caceres G, Puskas JA and Magliocco AM: Circulating tumor cells: A window into tumor development and therapeutic effectiveness. Cancer Control. 22:167–176. 2015. View Article : Google Scholar : PubMed/NCBI

56 

Caixeiro NJ, Kienzle N, Lim SH, Spring KJ, Tognela A, Scott KF, de Souza P and Becker TM: Circulating tumour cells-a bona fide cause of metastatic cancer. Cancer Metastasis Rev. 33:747–756. 2014. View Article : Google Scholar : PubMed/NCBI

57 

Sceneay J, Smyth MJ and Möller A: The pre-metastatic niche: Finding common ground. Cancer Metastasis Rev. 32:449–464. 2013. View Article : Google Scholar : PubMed/NCBI

58 

Paduch R: The role of lymphangiogenesis and angiogenesis in tumor metastasis. Cell Oncol (Dordr). 39:397–410. 2016. View Article : Google Scholar : PubMed/NCBI

59 

Coso S, Bovay E and Petrova TV: Pressing the right buttons: Signaling in lymphangiogenesis. Blood. 123:2614–2624. 2014. View Article : Google Scholar : PubMed/NCBI

60 

Pietras K and Östman A: Hallmarks of cancer: Interactions with the tumor stroma. Exp Cell Res. 316:1324–1331. 2010. View Article : Google Scholar : PubMed/NCBI

61 

Spano D and Zollo M: Tumor microenvironment: A main actor in the metastasis process. Clin Exp Metastasis. 29:381–395. 2012. View Article : Google Scholar : PubMed/NCBI

62 

Spinella F, Caprara V, Cianfrocca R, Rosanò L, Di Castro V, Garrafa E, Natali PG and Bagnato A: The interplay between hypoxia, endothelial and melanoma cells regulates vascularization and cell motility through endothelin-1 and vascular endothelial growth factor. Carcinogenesis. 35:840–848. 2014. View Article : Google Scholar : PubMed/NCBI

63 

Re RN and Cook JL: An intracrine view of angiogenesis. Bioessays. 28:943–953. 2006. View Article : Google Scholar : PubMed/NCBI

64 

Egeblad M, Nakasone ES and Werb Z: Tumors as organs: Complex tissues that interface with the entire organism. Dev Cell. 18:884–901. 2010. View Article : Google Scholar : PubMed/NCBI

65 

Wolf D, Sopper S, Pircher A, Gastl G and Wolf AM: Treg(s) in cancer: Friends or foe? J Cell Physiol. 230:2598–2605. 2015. View Article : Google Scholar : PubMed/NCBI

66 

Nishikawa H and Sakaguchi S: Regulatory T cells in tumor immunity. Int J Cancer. 127:759–767. 2010.PubMed/NCBI

67 

Bhatia A and Kumar Y: Cellular and molecular mechanisms in cancer immune escape: A comprehensive review. Expert Rev Clin Immunol. 10:41–62. 2014. View Article : Google Scholar : PubMed/NCBI

68 

Dyck L and Mills KHG: Immune checkpoints and their inhibition in cancer and infectious diseases. Eur J Immunol. 47:765–779. 2017. View Article : Google Scholar : PubMed/NCBI

69 

Curiel TJ: Regulatory T cells and treatment of cancer. Curr Opin Immunol. 20:241–246. 2008. View Article : Google Scholar : PubMed/NCBI

70 

deLeeuw RJ, Kost SE, Kakal JA and Nelson BH: The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: A critical review of the literature. Clin Cancer Res. 18:3022–3029. 2012. View Article : Google Scholar : PubMed/NCBI

71 

Mailloux AW and Young MR: Regulatory T-cell trafficking: From thymic development to tumor-induced immune suppression. Crit Rev Immunol. 30:435–447. 2010. View Article : Google Scholar : PubMed/NCBI

72 

De Visser KE, Eichten A and Coussens LM: Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 6:24–37. 2006. View Article : Google Scholar : PubMed/NCBI

73 

Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013. View Article : Google Scholar : PubMed/NCBI

74 

Josefowicz SZ, Lu LF and Rudensky AY: Regulatory T cells: Mechanisms of differentiation and function. Annu Rev Immunol. 30:531–564. 2012. View Article : Google Scholar : PubMed/NCBI

75 

Struchko GY, Меrkulova LМ and Moskvichev YV: Morphological and immunohistochemical characteristics of the thymus during chemical carcinogenesis induced by 1,2-dimethylhydrazine administration. Morfologiia. 146:35–39. 2014.(In Russian). PubMed/NCBI

76 

Hamidinia M, Ghafourian Boroujerdnia M, Talaiezadeh A, Solgi G, Roshani R, Iranprast S and Khodadadi A: Increased P-35, EBI3 transcripts and other Treg markers in peripheral blood mononuclear cells of breast cancer patients with different clinical stages. Adv Pharm Bull. 5:261–267. 2015. View Article : Google Scholar : PubMed/NCBI

77 

Lee JH, Chen Y, Chan JL, Qian YW and Goydos JS: Molecular analysis of melanoma-induced sentinel lymph node immune dysfunction. Cancer Immunol Immunother. 60:685–692. 2011. View Article : Google Scholar : PubMed/NCBI

78 

Lagios MD: Clinical significance of immunohistochemically detectable epithelial cells in sentinel lymph node and bone marrow in breast cancer. J Surg Oncol. 83:1–4. 2003. View Article : Google Scholar : PubMed/NCBI

79 

Vasco C, Canazza A, Rizzo A, Mossa A, Corsini E, Silvani A, Fariselli L, Salmaggi A and Ciusani E: Circulating T regulatory cells migration and phenotype in glioblastoma patients: An in vitro study. J Neurooncol. 115:353–363. 2013. View Article : Google Scholar : PubMed/NCBI

80 

Zhang X, Kelaria S, Kerstetter J and Wang J: The functional and prognostic implications of regulatory T cells in colorectal carcinoma. J Gastrointest Oncol. 6:307–313. 2015.PubMed/NCBI

81 

Protti MP, De Monte L and Di Lullo G: Tumor antigen-specific CD4+ T cells in cancer immunity: From antigen identification to tumor prognosis and development of therapeutic strategies. Tissue Antigens. 83:237–246. 2014. View Article : Google Scholar : PubMed/NCBI

82 

Chen X and Oppenheim JJ: Resolving the identity myth: Key markers of functional CD4+FoxP3+ regulatory T cells. Int Immunopharmacol. 11:1489–1496. 2011. View Article : Google Scholar : PubMed/NCBI

83 

Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B, Fumoleau P and Ghiringhelli F: Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating Foxp3+ regulatory T cells. Clin Cancer Res. 14:2413–2420. 2008. View Article : Google Scholar : PubMed/NCBI

84 

Teng MW, Ngiow SF, von Scheidt B, McLaughlin N, Sparwasser T and Smyth MJ: Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res. 70:7800–7809. 2010. View Article : Google Scholar : PubMed/NCBI

85 

Liu Y, Gu Y and Cao X: The exosomes in tumor immunity. Oncoimmunology. 4:e10274722015. View Article : Google Scholar : PubMed/NCBI

86 

Bersanelli M and Buti S: From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis. World J Clin Oncol. 8:37–53. 2017. View Article : Google Scholar : PubMed/NCBI

87 

Dolan DE and Gupta S: PD-1 pathway inhibitors: Changing the landscape of cancer immunotherapy. Cancer Control. 21:231–237. 2014. View Article : Google Scholar : PubMed/NCBI

88 

Rei M, Pennington DJ and Silva-Santos B: The emerging protumor role of γδ T lymphocytes: Implications for cancer immunotherapy. Cancer Res. 75:798–802. 2015. View Article : Google Scholar : PubMed/NCBI

89 

Pennock GK and Chow LQ: The evolving role of immune checkpoint inhibitors in cancer treatment. Oncologist. 20:812–822. 2015. View Article : Google Scholar : PubMed/NCBI

90 

Zhu J, Powis de Tenbossche CG, Cane S, Colau D, van Baren N, Lurquin C, Schmitt-Verhulst AM, Liljestrom P, Uyttenhove C and Van den Eynde BJ: Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes. Nat Commun. 8:14042017. View Article : Google Scholar : PubMed/NCBI

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APA
Lisovska, N., & Lisovska, N. (2019). Tumor progression mechanisms: Insights from the central immune regulation of tissue homeostasis (Review). Oncology Letters, 17, 5311-5318. https://doi.org/10.3892/ol.2019.10218
MLA
Lisovska, N., Shanazarov, N."Tumor progression mechanisms: Insights from the central immune regulation of tissue homeostasis (Review)". Oncology Letters 17.6 (2019): 5311-5318.
Chicago
Lisovska, N., Shanazarov, N."Tumor progression mechanisms: Insights from the central immune regulation of tissue homeostasis (Review)". Oncology Letters 17, no. 6 (2019): 5311-5318. https://doi.org/10.3892/ol.2019.10218