Highlights
- •Cytotoxic T-Lymphocytes increase in patients with non-adenocarcinoma, but not with adenocarcinoma.
- •Tumour microenvironment is immunosuppressive in non-smokers with lung adenocarcinoma.
- •CD8+GATA3+ and CD8+FOXP3+ T cells infiltrate adenocarcinoma in non-smokers.
- •M2-like macrophages and effector Tregs increase in non-smokers with adenocarcinoma.
- •Immunosuppressive microenvironment in adenocarcinoma determines poor prognosis.
Abstract
We have previously demonstrated that the prognostic significance of tumour-infiltrating
CD8+ T cells significantly differs according to histological type and patient smoking
habits in non-small cell lung cancer (NSCLC). This work suggested that infiltrating
CD8+ T cells may not be activated sufficiently in the immunosuppressive microenvironment
in non-smokers with adenocarcinoma. To understand the immunogenic microenvironment
in NSCLC, we characterised immune cells comprehensively by performing an immunohistochemical
evaluation using an alternative counting method and multicolour staining method (n = 234),
and assessed immune-related gene expression by using genetic analytical approaches
(n = 58). We found that high infiltration of activated CD8+ T cells expressing interferon gamma (IFN-γ) and granzyme was correlated with postoperative
survival in patients with non-adenocarcinoma. On the contrary, CD8+ T-cell accumulation was identified as a worse prognostic factor in patients with
adenocarcinoma, particularly in non-smokers. Infiltrating CD8+ T cells were significantly less activated in this microenvironment with high expression
of various immunoregulation genes. Potentially immunoregulatory CD8+ FOXP3+ T cells and immunodysfunctional CD8+ GATA3+ T cells were increased in adenocarcinoma of non-smokers. CD4+ FOXP3+ regulatory T cells expressing chemokine receptor-4 (CCR4)- and chemokine ligand (CCL17)-expressing
CD163+ M2-like macrophages also accumulated correlatively and significantly in adenocarcinoma
of non-smokers. These characteristic immune cells may promote tumour progression possibly
by creating an immunosuppressive microenvironment in non-smoking patients with lung
adenocarcinoma. Our findings may be helpful for refining the current strategy of personalised
immunotherapy including immune-checkpoint blockade therapy for NSCLC.
Keywords
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Article info
Publication history
Published online: September 23, 2017
Accepted:
August 23,
2017
Received in revised form:
August 9,
2017
Received:
June 8,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
