Obesity and cancer: the gammadelta T cell link

Ilan Bank

Exploration of Immunology ›› 2022, Vol. 2 ›› Issue (3) : 320 -333.

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Exploration of Immunology ›› 2022, Vol. 2 ›› Issue (3) :320 -333. DOI: 10.37349/ei.2022.00053
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Obesity and cancer: the gammadelta T cell link
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Abstract

Obesity has become a worldwide scourge, affecting more than 10% of adults worldwide. While widely recognized to be associated with increased incidence of medical conditions such as diabetes mellitus and atherosclerosis, obesity also accounts for 9% of the cancer burden in some populations. This is due in part to perturbation of protective immune mechanisms involving natural killer cells, macrophages, and neutrophils. Recent studies indicate that γδ T cells play a prominent protective role against cancer, but in some circumstances are detrimental and pro tumorogenic. In this review, the current scientific literature was explored to determine whether and how obesity affects the anti- and pro-tumoral functions of γδ T cells. Considerable perturbations of γδ T cells by obesity were revealed, suggesting that the “obesity-γδ T cell axis” may profoundly impact the increased incidence of cancer in obese individuals and is worthy of further study.

Keywords

Gammadelta T cells / obesity / interleukin-17 / cancer

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Ilan Bank. Obesity and cancer: the gammadelta T cell link. Exploration of Immunology, 2022, 2 (3) : 320-333 DOI:10.37349/ei.2022.00053

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References

[1]

Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K ; International Agency for Research on Cancer Handbook Working Group. Body fatness and cancer-viewpoint of the IARC working group. N Engl J Med. 2016; 375: 794-8.

[2]

Crudele L, Piccinin E, Moschetta A. Visceral adiposity and cancer: role in pathogenesis and prognosis. Nutrients. 2021; 13: 2101.

[3]

Endo Y, Yokote K, Nakayama T. The obesity-related pathology and Th17 cells. Cell Mol Life Sci. 2017; 74: 1231-45.

[4]

Farag KI, Makkouk A, Norian LA. Re-evaluating the effects of obesity on cancer immunotherapy outcomes in renal cancer: what do we really know? Front Immunol. 2021; 12: 668494.

[5]

Boulenouar S, Michelet X, Duquette D, Alvarez D, Hogan AE, Dold C, et al. Adipose type one innate lymphoid cells regulate macrophage homeostasis through targeted cytotoxicity. Immunity. 2017; 46: 273-86.

[6]

Abuzakouk M, Feighery C, Kelleher D, O’Briain DS, Jones E, Weir D, et al. Increased HLA-DR and CD44 antigen expression in the gut: evidence of extraarticular immunological activity in rheumatoid arthritis. J Rheumatol. 1999; 26: 1869-76.

[7]

Jahn J, Spielau M, Brandsch C, Stangl GI, Delank KS, Bähr I, et al. Decreased NK cell functions in obesity can be reactivated by fat mass reduction. Obesity (Silver Spring). 2015; 23: 2233-41.

[8]

Bank I, DePinho RA, Brenner MB, Cassimeris J, Alt FW, Chess L. A functional T3 molecule associated with a novel heterodimer on the surface of immature human thymocytes. Nature. 1986; 322: 179-81.

[9]

Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, et al. Identification of a putative second T-cell receptor. Nature. 1986; 322: 145-9.

[10]

Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature. 1984; 312: 36-40.

[11]

Criscitiello MF, Ohta Y, Saltis M, McKinney EC, Flajnik MF. Evolutionarily conserved TCR binding sites, identification of T cells in primary lymphoid tissues, and surprising trans-rearrangements in nurse shark. J Immunol. 2010; 184: 6950-60.

[12]

Chien YH, Meyer C, Bonneville M. γδ T cells: first line of defense and beyond. Annu Rev Immunol. 2014; 32: 121-55.

[13]

Hayday AC. γδ T cell update: adaptate orchestrators of immune surveillance. J Immunol. 2019; 203: 311-20.

[14]

Vantourout P, Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nat Rev Immunol. 2013; 13: 88-100.

[15]

Gully BS, Rossjohn J, Davey MS. Our evolving understanding of the role of the γδ T cell receptor in γδ T cell mediated immunity. Biochem Soc Trans. 2021; 49: 1985-95.

[16]

Melandri D, Zlatareva I, Chaleil RAG, Dart RJ, Chancellor A, Nussbaumer O, et al. The γδTCR combines innate immunity with adaptive immunity by utilizing spatially distinct regions for agonist selection and antigen responsiveness. Nat Immunol. 2018; 19: 1352-65.

[17]

Silva-Santos B, Mensurado S, Coffelt SB . γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer. Nat Rev Cancer. 2019; 19: 392-404.

[18]

Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015; 21: 938-45.

[19]

Holmen Olofsson G, Idorn M, Carnaz Simões AM, Aehnlich P, Skadborg SK, Noessner E, et al. Vγ9Vδ2 T cells concurrently kill cancer cells and cross-present tumor antigens. Front Immunol. 2021; 12: 645131.

[20]

Chabab G, Barjon C, Bonnefoy N, Lafont V. Pro-tumor γδ T cells in human cancer: polarization, mechanisms of action, and implications for therapy. Front Immunol. 2020; 11: 2186.

[21]

Ma C, Zhang Q, Ye J, Wang F, Zhang Y, Wevers E, et al. Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer. J Immunol. 2012; 189: 5029-36.

[22]

Peng G, Wang HY, Peng W, Kiniwa Y, Seo KH, Wang RF. Tumor-infiltrating γδ T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity. 2007; 27: 334-48.

[23]

Daley D, Zambirinis CP, Seifert L, Akkad N, Mohan N, Werba G, et al. γδ T cells support pancreatic oncogenesis by restraining αβ T cell activation. Cell. 2016; 166: 1485-99.e15.

[24]

Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, et al. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015; 522: 345-8.

[25]

Oberg HH, Wesch D, Kalyan S, Kabelitz D. Regulatory interactions between neutrophils, tumor cells and T cells. Front Immunol. 2019; 10: 1690.

[26]

McAllister F, Bailey JM, Alsina J, Nirschl CJ, Sharma R, Fan H, et al. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia. Cancer Cell. 2014; 25: 621-37.

[27]

Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A, Hu B, et al. Commensal microbiota promote lung cancer development via γδ T cells. Cell. 2019; 176: 998-1013.e16.

[28]

Majumder S, McGeachy MJ. IL-17 in the pathogenesis of disease: good intentions gone awry. Annu Rev Immunol. 2021; 39: 537-56.

[29]

Gislette T, Chen J. The possible role of IL-17 in obesity-associated cancer. ScientificWorldJournal. 2010; 10: 2265-71.

[30]

Oliveira BM, Rasteiro AM, Correia A, Pinto A, Meireles P, Ferreira PG, et al. T cells in mesenteric and subcutaneous adipose tissue of Holstein-Friesian cows. Sci Rep. 2019; 9: 3413.

[31]

Zúñiga LA, Shen WJ, Joyce-Shaikh B, Pyatnova EA, Richards AG, Thom C, et al. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol. 2010; 185: 6947-59.

[32]

Kohlgruber AC, Gal-Oz ST, LaMarche NM, Shimazaki M, Duquette D, Koay HF, et al. γδ T cells producing interleukin-17A regulate adipose regulatory T cell homeostasis and thermogenesis. Nat Immunol. 2018; 19: 464-74.

[33]

Hu B, Jin C, Zeng X, Resch JM, Jedrychowski MP, Yang Z, et al. γδ T cells and adipocyte IL-17RC control fat innervation and thermogenesis. Nature. 2020; 578: 610-4.

[34]

Goldberg EL, Shchukina I, Asher JL, Sidorov S, Artyomov MN, Dixit VD. Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue. Nat Metab. 2020; 2: 50-61.

[35]

He S, Kahles F, Rattik S, Nairz M, McAlpine CS, Anzai A, et al. Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease. Nature. 2019; 566: 115-9.

[36]

Caspar-Bauguil S, Cousin B, Galinier A, Segafredo C, Nibbelink M, André M, et al. Adipose tissues as an ancestral immune organ: site-specific change in obesity. FEBS Lett. 2005; 579: 3487-92.

[37]

Caspar-Bauguil S, Cousin B, André M, Nibbelink M, Galinier A, Periquet B, et al. Weight-dependent changes of immune system in adipose tissue: importance of leptin. Exp Cell Res. 2006; 312: 2195-202.

[38]

Tougaard P, Martinsen LO, Lützhøft DO, Jensen HE, Flethøj M, Vandenabeele P, et al. TL1A regulates adipose-resident innate lymphoid immune responses and enables diet-induced obesity in mice. Int J Obes (Lond). 2020; 44: 1062-74.

[39]

Mehta P, Nuotio-Antar AM, Smith CW. γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice. J Leukoc Biol. 2015; 97: 121-34.

[40]

Le Menn G, Sibille B, Murdaca J, Rousseau AS, Squillace R, Vergoni B, et al. Decrease in αβ/γδ T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation. FASEB J. 2019; 33: 2553-62.

[41]

Weinstock A, Moura Silva H, Moore KJ, Schmidt AM, Fisher EA. Leukocyte heterogeneity in adipose tissue, including in obesity. Circ Res. 2020; 126: 1590-612.

[42]

Taylor KR, Costanzo AE, Jameson JM. Dysfunctional γδ T cells contribute to impaired keratinocyte homeostasis in mouse models of obesity. J Invest Dermatol. 2011; 131: 2409-18.

[43]

Taylor KR, Mills RE, Costanzo AE, Jameson JM. γδ T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNFα in mouse models of obesity and metabolic disease. PLoS One. 2010; 5: e11422.

[44]

Munoz LD, Sweeney MJ, Jameson JM. Skin resident γδ T cell function and regulation in wound repair. Int J Mol Sci. 2020; 21: 9286.

[45]

Yu S, Wu X, Shi Z, Huynh M, Jena PK, Sheng L, et al. Diet-induced obesity exacerbates imiquimod-mediated psoriasiform dermatitis in anti-PD-1 antibody-treated mice: implications for patients being treated with checkpoint inhibitors for cancer. J Dermatol Sci. 2020; 97: 194-200.

[46]

Shibata S, Tada Y, Hau CS, Mitsui A, Kamata M, Asano Y, et al. Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells. Nat Commun. 2015; 6: 7687.

[47]

Ridaura VK, Bouladoux N, Claesen J, Chen YE, Byrd AL, Constantinides MG, et al. Contextual control of skin immunity and inflammation by Corynebacterium . J Exp Med. 2018; 215: 785-99.

[48]

Mathews JA, Krishnamoorthy N, Kasahara DI, Cho Y, Wurmbrand AP, Ribeiro L, et al. IL-33 drives augmented responses to ozone in obese mice. Environ Health Perspect. 2017; 125: 246-53.

[49]

Mathews JA, Wurmbrand AP, Ribeiro L, Neto FL, Shore SA. Induction of IL-17A precedes development of airway hyperresponsiveness during diet-induced obesity and correlates with complement factor D. Front Immunol. 2014; 5: 440.

[50]

Soares A, Beraldi EJ, Ferreira PE, Bazotte RB, Buttow NC. Intestinal and neuronal myenteric adaptations in the small intestine induced by a high-fat diet in mice. BMC Gastroenterol. 2015; 15: 3.

[51]

Park C, Cheung KP, Limon N, Costanzo A, Barba C, Miranda N, et al. Obesity modulates intestinal intraepithelial T cell persistence, CD103 and CCR9 expression, and outcome in dextran sulfate sodium-induced colitis. J Immunol. 2019; 203: 3427-35.

[52]

Yusta B, Baggio LL, Koehler J, Holland D, Cao X, Pinnell LJ, et al. GLP-1R agonists modulate enteric immune responses through the intestinal intraepithelial lymphocyte GLP-1R. Diabetes. 2015; 64: 2537-49.

[53]

Zhao Z, Xu P, Jie Z, Zuo Y, Yu B, Soong L, et al. γδ T cells as a major source of IL-17 production during age-dependent RPE degeneration. Invest Ophthalmol Vis Sci. 2014; 55: 6580-9.

[54]

Tie G, Yan J, Khair L, Messina JA, Deng A, Kang J, et al. Hypercholesterolemia increases colorectal cancer incidence by reducing production of NKT and γδ T cells from hematopoietic stem cells. Cancer Res. 2017; 77: 2351-62.

[55]

Baek AE, Yu YA, He S, Wardell SE, Chang CY, Kwon S, et al. The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun. 2017; 8: 864.

[56]

Wunderlich CM, Ackermann PJ, Ostermann AL, Adams-Quack P, Vogt MC, Tran ML, et al. Obesity exacerbates colitis-associated cancer via IL-6-regulated macrophage polarisation and CCL-20/CCR-6-mediated lymphocyte recruitment. Nat Commun. 2018; 9: 1646.

[57]

Lopes N, McIntyre C, Martin S, Raverdeau M, Sumaria N, Kohlgruber AC, et al. Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments. Nat Immunol. 2021; 22: 179-92.

[58]

Costanzo AE, Taylor KR, Dutt S, Han PP, Fujioka K, Jameson JM. Obesity impairs γδ T cell homeostasis and antiviral function in humans. PLoS One. 2015; 10: e0120918.

[59]

Li Y, Woods K, Parry-Strong A, Anderson RJ, Capistrano C, Gestin A, et al. Distinct dysfunctional states of circulating innate-like T cells in metabolic disease. Front Immunol. 2020; 11: 448.

[60]

Staats R, Rodrigues R, Barros A, Bacelar-Nicolau L, Aguiar M, Fernandes D, et al. Decrease of perforin positive CD3+ γδ-T cells in patients with obstructive sleep disordered breathing . Sleep Breath. 2018; 22: 211-21.

[61]

Donninelli G, Del Cornò M, Pierdominici M, Scazzocchio B, Varìư R, Varano B, et al. Distinct blood and visceral adipose tissue regulatory T cell and innate lymphocyte profiles characterize obesity and colorectal cancer. Front Immunol. 2017; 8: 643.

[62]

Xu C, Mathews AE, Rodrigues C, Eudy BJ, Rowe CA, O’Donoughue A, et al. Aged garlic extract supplementation modifies inflammation and immunity of adults with obesity: a randomized, double-blind, placebo-controlled clinical trial. Clin Nutr ESPEN. 2018; 24: 148-55.

[63]

Mogilenko DA, Caiazzo R, L’Homme L, Pineau L, Raverdy V, Noulette J, et al. IFNγ-producing NK cells in adipose tissue are associated with hyperglycemia and insulin resistance in obese women. Int J Obes (Lond). 2021; 45: 1607-17.

[64]

Looman KIM, Santos S, Moll HA, Leijten CWE, Grosserichter-Wagener C, Voortman T, et al. Childhood adiposity associated with expanded effector memory CD8+ and Vδ2+Vγ9+ T cells . J Clin Endocrinol Metab. 2021; 106: e3923-35.

[65]

Melo AM, Mylod E, Fitzgerald V, Donlon NE, Murphy DM, Foley EK, et al. Tissue distribution of γδ T cell subsets in oesophageal adenocarcinoma. Clin Immunol. 2021; 229: 108797.

[66]

Lu Z, Meng L, Sun Z, Shi X, Shao W, Zheng Y, et al. Differentially expressed genes and enriched signaling pathways in the adipose tissue of obese people. Front Genet. 2021; 12: 620740.

[67]

Del Cornò M, D’Archivio M, Conti L, Scazzocchio B, Varìư R, Donninelli G, et al. Visceral fat adipocytes from obese and colorectal cancer subjects exhibit distinct secretory and ω6 polyunsaturated fatty acid profiles and deliver immunosuppressive signals to innate immunity cells. Oncotarget. 2016; 7: 63093-105.

[68]

Shalapour S, Karin M. Pas de deux: control of anti-tumor immunity by cancer-associated inflammation. Immunity. 2019; 51: 15-26.

[69]

Faustino LD, Griffith JW, Rahimi RA, Nepal K, Hamilos DL, Cho JL, et al. Interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung. Nat Immunol. 2020; 21: 1371-83.

[70]

Wu J, Chen Z, Wickström SL, Gao J, He X, Jing X, et al. Interleukin-33 is a novel immunosuppressor that protects cancer cells from TIL killing by a macrophage-mediated shedding mechanism. Adv Sci (Weinh). 2021; 8: e2101029.

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