Abstract
Innate lymphoid cells (ILCs) are important for both tissue immunity and tissue homeostasis. They are classified into three groups: Group 1 ILCs include NK cells, which are important in eliciting immunity against intracellular pathogens; group 2 ILCs protect against parasitic helminths; and group 3 ILCs protect against extracellular pathogens. The role of ILCs in cancer immunity remains unclear. In this chapter, we discuss methods for isolating and characterizing tumor-infiltrating ILC subsets within the tumor microenvironment in an experimental murine model of B16 melanoma. The chapter also highlights the expression of PD-1 on the various ILC subsets within the tumor microenvironment.
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References
Salimi M, Barlow JL, Saunders SP et al (2013) A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med 210(13):2939–2950
Geremia A, Arancibia-Carcamo CV, Fleming MP et al (2011) IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease. J Exp Med 208(6):1127–1133
Spits H, Artis D, Colonna M et al (2013) Innate lymphoid cells—a proposal for uniform nomenclature. Nat Rev Immunol 13(2):145–149
Crellin NK, Trifari S, Kaplan CD et al (2010) Regulation of cytokine secretion in human CD127(+) LTi-like innate lymphoid cells by Toll-like receptor 2. Immunity 33(5):752–764
Herberman RB, Nunn ME, Holden HT et al (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer 16(2):230–239
Weizman OE, Adams NM, Schuster IS et al (2017) ILC1 confer early host protection at initial sites of viral infection. Cell 171(4):795–808.e12
Klose CSN, Kiss EA, Schwierzeck V et al (2014) Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157(2):340–356
Neill DR, Wong SH, Bellosi A et al (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464(7293):1367–1370
Huang Y, Guo L, Qiu J et al (2015) IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential ‘inflammatory’ type 2 innate lymphoid cells. Nat Immunol 16(2):161–169
Sanos SL, Bui VL, Mortha A et al (2009) RORgammat and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nat Immunol 10(1):83–91
Cella M, Fuchs A, Vermi W et al (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457(7230):722–725
Buonocore S, Ahern PP, Uhlig HH et al (2010) Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464(7293):1371–1375
Sonnenberg GF, Monticelli LA, Ellosi MM et al (2011) CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34(1):122–134
Takatori H, Kanno Y, Watford WT et al (2009) Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 206(1):35–41
Morvan MG, Lanier LL (2016) NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer 16(1):7–19
Martini M, Testi MG, Passetto M et al (2010) IFN-gamma-mediated upmodulation of MHC class I expression activates tumor-specific immune response in a mouse model of prostate cancer. Vaccine 28(20):3548–3557
Nakajima C, Uekusa Y, Iwasaki M et al (2001) A role of interferon-gamma (IFN-gamma) in tumor immunity: T cells with the capacity to reject tumor cells are generated but fail to migrate to tumor sites in IFN-gamma-deficient mice. Cancer Res 61(8):3399–3405
Beatty G, Paterson Y (2001) IFN-gamma-dependent inhibition of tumor angiogenesis by tumor-infiltrating CD4+ T cells requires tumor responsiveness to IFN-gamma. J Immunol 166(4):2276–2282
Larmonier N, Cathelin D, Larmonier C et al (2007) The inhibition of TNF-alpha anti-tumoral properties by blocking antibodies promotes tumor growth in a rat model. Exp Cell Res 313(11):2345–2355
Jovanovic IP, Pejnovic N, Radosavljevic GD et al (2014) Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int J Cancer 134(7):1669–1682
Molofsky AB, Nussbaum JC, Liang HE et al (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210(3):535–549
Huber S, Gagliani N, Zenewicz LA et al (2012) IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491(7423):259–263
Chan IH, Jain R, Tessmer MS et al (2014) Interleukin-23 is sufficient to induce rapid de novo gut tumorigenesis, independent of carcinogens, through activation of innate lymphoid cells. Mucosal Immunol 7(4):842–856
Schatton T, Murphy GF, Frank NY et al (2008) Identification of cells initiating human melanomas. Nature 451(7176):345–349
Acknowledgments
We would like to thank the Academy of Medical Sciences, Springboard Award [SBF003\1129] supported by Wellcome Trust and Newcastle University Research Fellowship for supporting this work. G.M. is supported by a Medical Research Council [MRC] Discovery Medicine North Ph.D. studentship. M.P. is supported by a Wellcome Trust Vacation Scholarship [216503/Z/19/Z].
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Mallett, G., Patterson, W., Payne, M., Amarnath, S. (2020). Isolation and Characterization of Innate Lymphoid Cells within the Murine Tumor Microenvironment. In: Amarnath, S. (eds) Innate Lymphoid Cells . Methods in Molecular Biology, vol 2121. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0338-3_14
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DOI: https://doi.org/10.1007/978-1-0716-0338-3_14
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