Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Activated innate lymphoid cell populations accumulate in human tumour tissues

Authors: Maryam Salimi, Ruozheng Wang, Xuan Yao, Xi Li, Xiyan Wang, Yuhui Hu, Xumei Chang, Peiwen Fan, Tao Dong, Graham Ogg

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Innate lymphoid cells (ILC) are part of a heterogeneous family of haematopoietic effector cells which lack re-arranged antigen-specific receptors. They promote host defense and contribute to tissue and metabolic homeostasis, wound healing and immune surveillance. Their role in human cancer immunity is less defined, and therefore we aimed to identify the frequency and phenotype of distinct ILC groups in various types of cancer.

Methods

Tissue samples and peripheral blood were collected from patients undergoing surgical resection of gastrointestinal and breast tumours. Single cell suspension of tumour tissue was immediately obtained following surgery using tumour dissociation.

Results

We observed significantly higher frequencies of ILC2 (p value: 0.04) in malignant breast cancer tissue and significantly higher frequencies of group 1 ILC (p value: 0.001) in malignant gastrointestinal tumours. Tumour infiltrating ILC were found to show an activated phenotype with higher expression of MHC-II, KLRG1, early activation marker CD69 and CD44.

Conclusions

Activated innate lymphoid cells infiltrate tumours dependent on tumour type and location.
Appendix
Available only for authorised users
Literature
1.
2.
Chow MT, Moller A, Smyth MJ. Inflammation and immune surveillance in cancer. Semin Cancer Biol. 2012;22(1):23–32.PubMedCrossRef
3.
4.
Pages F, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353(25):2654–66.PubMedCrossRef
5.
Coulie PG, et al. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer. 2014;14(2):135–46.PubMedCrossRef
6.
7.
8.
Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016;16(1):7–19.PubMedCrossRef
9.
Spits H, Bernink JH, Lanier L. NK cells and type 1 innate lymphoid cells: partners in host defense. Nat Immunol. 2016;17(7):758–64.PubMedCrossRef
10.
11.
Xue L, et al. Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol. 2014;133(4):1184–94.PubMedPubMedCentralCrossRef
12.
13.
Gronke K, Nielsen MK, Diefenbach A. Innate lymphoid cells, precursors and plasticity. Immunol Lett. 2016;
14.
15.
16.
Kirchberger S, 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.PubMedPubMedCentralCrossRef
17.
Bie Q, et al. Polarization of ILC2s in peripheral blood might contribute to immunosuppressive microenvironment in patients with gastric cancer. J Immunol Res. 2014; 2014: p. 923135
18.
Jovanovic IP, et al. Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int J Cancer. 2014;134(7):1669–82.PubMedCrossRef
19.
20.
van Beek JJP, et al. Innate Lymphoid Cells in Tumour Immunity. Biomedicines. 2016;4(1).
21.
22.
Carrega P, et al. The yin and Yang of innate lymphoid cells in Cancer. Immunol Lett. 2016;
23.
Goc J, Hepworth MR, Sonnenberg GF. Group 3 innate lymphoid cells: regulating host-commensal bacteria interactions in inflammation and cancer. Int Immunol. 2016;28(1):43–52.PubMed
24.
Zawlik I, et al. Immune checkpoints in aggressive breast cancer subtypes. Neoplasma. 2016;63(5)
25.
Bertucci F, et al. The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers. Oncoimmunology. 2016;5(3):e1085148.PubMedCrossRef
26.
Haanen JB, Robert C. Immune checkpoint inhibitors. Prog Tumor Res. 2015;42:55–66.PubMed
27.
28.
Chan TS, Khong PL, Kwong YL. Pembrolizumab and lenalidomide induced remission in refractory double-hit lymphoma. Ann Hematol; 2016;95(11):1917–8.
29.
Aoun F, et al. Checkpoint inhibitors in bladder and renal cancers: results and perspectives. Immunotherapy. 2015;7(12):1259–71.PubMedCrossRef
30.
Webster RM. The immune checkpoint inhibitors: where are we now? Nat Rev Drug Discov. 2014;13(12):883–4.PubMedCrossRef
31.
McCoy KD, Le Gros G. The role of CTLA-4 in the regulation of T cell immune responses. Immunol Cell Biol. 1999;77(1):1–10.PubMedCrossRef
32.
Theurich S, et al. Local tumor treatment in combination with systemic Ipilimumab immunotherapy prolongs overall survival in patients with advanced malignant melanoma. Cancer Immunol Res. 2016;4(9):744–54.PubMedCrossRef
33.
Oliphant CJ, et al. MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity. 2014;41(2):283–95.PubMedPubMedCentralCrossRef
34.
Mirchandani AS, et al. Type 2 innate lymphoid cells drive CD4+ Th2 cell responses. J Immunol. 2014;192(5):2442–8.PubMedCrossRef
35.
36.
Voehringer D, Koschella M, Pircher H. Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood. 2002;100(10):3698–702.PubMedCrossRef
37.
Ouyang Q, et al. Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1). Exp Gerontol. 2003;38(8):911–20.PubMedCrossRef
38.
Kobayashi T, et al. NKT cell-targeted vaccination plus anti-4-1BB antibody generates persistent CD8 T cell immunity against B cell lymphoma. Oncoimmunology. 2015;4(3):e990793.PubMedPubMedCentralCrossRef
39.
Huang Y, et al. IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol. 2015;16(2):161–9.PubMedCrossRef
40.
41.
Malaise M, et al. KLRG1+ NK cells protect T-bet-deficient mice from pulmonary metastatic colorectal carcinoma. J Immunol. 2014;192(4):1954–61.PubMedCrossRef
42.
Shiow LR, et al. CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature. 2006;440(7083):540–4.PubMedCrossRef
43.
44.
Mackley EC, et al. CCR7-dependent trafficking of RORgamma(+) ILC creates a unique microenvironment within mucosal draining lymph nodes. Nat Commun. 2015;6:5862.PubMedPubMedCentralCrossRef
45.
Xu H, et al. IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol. 2012;5(6):658–69.PubMedPubMedCentralCrossRef
46.
Bernink JH, et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol. 2013;14(3):221–9.PubMedCrossRef
47.
Munneke JM, et al. Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood. 2014;124(5):812–21.PubMedCrossRef
48.
49.
Termeer C, et al. Targeting dendritic cells with CD44 monoclonal antibodies selectively inhibits the proliferation of naive CD4+ T-helper cells by induction of FAS-independent T-cell apoptosis. Immunology. 2003;109(1):32–40.PubMedPubMedCentralCrossRef
50.
Bartemes KR, et al. IL-33-responsive lineage- CD25+ CD44(hi) lymphoid cells mediate innate type 2 immunity and allergic inflammation in the lungs. J Immunol. 2012;188(3):1503–13.PubMedCrossRef
51.
Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002;13(2):95–109.PubMedCrossRef
52.
Xu X, et al. IFN-gamma induces cell growth inhibition by Fas-mediated apoptosis: requirement of STAT1 protein for up-regulation of Fas and FasL expression. Cancer Res. 1998;58(13):2832–7.PubMed
53.
Eberl G, MacDonald HR. Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells. Eur J Immunol. 2000;30(4):985–92.PubMedCrossRef
54.
Lu B, Yang M, Wang Q. Interleukin-33 in tumorigenesis, tumor immune evasion, and cancer immunotherapy. J Mol Med (Berl). 2016;94(5):535–43.CrossRef
55.
Gurusamy D, et al. A role for IL-13 in the progression of prostate tumors (TUM10P.1046). J Immunol. 2015;194(1 Supplement)):211–27.
56.
Dhakal M, et al. IL-13Ralpha1 is a surface marker for M2 macrophages influencing their differentiation and function. Eur J Immunol. 2014;44(3):842–55.PubMedPubMedCentralCrossRef
57.
Carrega P, et al. NCR(+)ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures. Nat Commun. 2015;6:8280.PubMedCrossRef
Metadata
Title
Activated innate lymphoid cell populations accumulate in human tumour tissues
Authors
Maryam Salimi
Ruozheng Wang
Xuan Yao
Xi Li
Xiyan Wang
Yuhui Hu
Xumei Chang
Peiwen Fan
Tao Dong
Graham Ogg
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4262-4

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Technical advance

An advanced glioma cell invasion assay based on organotypic brain slice cultures

Study protocol

The PiGeOn project: protocol of a longitudinal study examining psychosocial and ethical issues and outcomes in germline genomic sequencing for cancer

Research article

Loss of expression and prognosis value of alpha-internexin in gastroenteropancreatic neuroendocrine neoplasm

Research article

Overall survival and time trends in breast and cervical cancer incidence and mortality in the Regional Health District (RHD) of Barretos, São Paulo, Brazil

Research article

Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations

Research article

Endogenous H2S producing enzymes are involved in apoptosis induction in clear cell renal cell carcinoma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits