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. 2018 Mar 27;18(1):341.
doi: 10.1186/s12885-018-4262-4.

Activated innate lymphoid cell populations accumulate in human tumour tissues

Maryam Salimi  1 , Ruozheng Wang  2   3 , Xuan Yao  1 , Xi Li  1 , Xiyan Wang  2   3 , Yuhui Hu  2   3 , Xumei Chang  2   3 , Peiwen Fan  2   3 , Tao Dong  1   2   3   4 , Graham Ogg  5   6   7
Affiliations

Activated innate lymphoid cell populations accumulate in human tumour tissues

Maryam Salimi et al. BMC Cancer. .

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.

Keywords: Breast cancer; Gastrointestinal cancer; Immune checkpoint; Innate lymphoid cells.

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Conflict of interest statement

Ethics approval and consent to participate

Written ethical approval was obtained from Xinjiang Tumour Hospital ethical committee and Oxford Tropical Research Ethics Committee (587–16) and London - City & East Research Ethics Committee (16/LO/1607). All participants gave informed written consent to participate.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Frequency of ILC populations in breast and GI tumours. Percentage of lineage negative CD45 positive ILC groups in benign (n = 4) and malignant breast tumours (n = 17) determined by flow cytometry (a), PBMCs from patients with benign (n = 4) and malignant (n = 15) breast tumours (b), lesional (n = 15) and para-lesional (n = 15) gastrointestinal tumour tissues (c). Frequency of ILC1, ILC2 and ILC3 is shown as the percentage of lineage negative, CD56−, CD45+ and NK cells are gated from lineage negative, CD45+ cells
Fig. 2
Fig. 2
Expression of PD1 and CTLA-4 on ILC populations. Expression of PD1 (a left graph) and CTLA-4 (a right graph) on ILC groups in peripheral blood of patients with malignant breast tumour (n = 14–16), benign breast tumour tissue (n = 4) and malignant breast tumour tissue (n = 14–16) determined by flow cytometry. Expression of PD1 (b left graph) and CTLA-4 (b right graph) on ILC groups in peripheral blood of patients with malignant GI tumour (n = 8–12), para-lesional tumour tissue (n = 8–12) and malignant GI tumour tissue (n = 8–12)
Fig. 3
Fig. 3
Expression of MHC II and Klrg1 on ILC populations. Expression of MHC II (a left graph) and Klrg1 (b left graph) on ILC groups in peripheral blood of patients with malignant breast tumour (n = 16–17), benign breast tumour tissue (n = 4) and malignant breast tumour tissue (n = 16–17) determined by flow cytometry. Expression of MHC II (a right graph) and Klrg1 (b right graph) on ILC groups in peripheral blood of patients with malignant GI tumour (n = 9–12), para-lesional tumour tissue (n = 9–12) and malignant GI tumour tissue (n = 9–12)
Fig. 4
Fig. 4
Expression of CD69, CCR7 and CD44 on ILC populations. Expression of CD69 (a left graph), CCR7 (b left graph) and CD44 (c left graph) on ILC groups in peripheral blood of patients with malignant breast tumour (n = 14–17), benign breast tumour tissue (n = 4) and malignant breast tumour tissue (n = 14–17) determined by flow cytometry. Expression of CD69 (a right graph), CCR7 (b right graph) and CD44 (c right graph) on ILC groups in peripheral blood of patients with malignant GI tumour (n = 9–13), para-lesional tumour tissue (n = 9–13) and malignant GI tumour tissue (n = 9–13)
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