Correlating tumor-infiltrating lymphocytes and lung cancer stem cells: a cross-sectional study.

Tumor-infiltrating lymphocytes (TILS) cancer stem cells (CSCs) cancer stem-like cells immunotherapy non-small cell lung cancer (NSCLC)

Journal

Annals of translational medicine
ISSN: 2305-5839
Titre abrégé: Ann Transl Med
Pays: China
ID NLM: 101617978

Informations de publication

Date de publication:
Nov 2019
Historique:
entrez: 14 1 2020
pubmed: 14 1 2020
medline: 14 1 2020
Statut: ppublish

Résumé

Lung cancer stem cells (LCSCs) are endowed with high aldehyde dehydrogenase (ALDH) expression and play roles in tumor proliferation, metastasis, and drug resistance. Their elusive nature may allow them to escape the immune response by tumor-infiltrating lymphocytes (TILs), which can positively affect the outcome in non-small cell lung cancer (NSCLC) patients. Despite independent investigations on both LCSCs and TILs, the relationship between the two has been very marginally considered. We analyzed whether these two cell types may be related as a prerequisite for novel diagnostic and therapeutic approaches. In this cross-sectional study, NSCLC human surgical specimens from 12 patients were tested by ALDEFLUOR assay to identify ALDH Statistically positive correlations were found between ALDH+ and CD8+, and between ALDH+ and CD3+ cells populations; no correlation was found between ALDH+ and CD4+ cells. The expression of CD3+ and CD8+ by cells accounted for 40.1% and 58.7%, respectively, of the variability of ALDH+ cell expression by an R-squared index, which highlights the strong correlation between TILs and LCSCs. Immunohistochemistry revealed 6-25% positive cells. We report a correlation between cytotoxic TILs and LCSCs, which may contribute to the future development of targeted therapies focusing on the different roles of lymphocytes against lung cancer.

Sections du résumé

BACKGROUND BACKGROUND
Lung cancer stem cells (LCSCs) are endowed with high aldehyde dehydrogenase (ALDH) expression and play roles in tumor proliferation, metastasis, and drug resistance. Their elusive nature may allow them to escape the immune response by tumor-infiltrating lymphocytes (TILs), which can positively affect the outcome in non-small cell lung cancer (NSCLC) patients. Despite independent investigations on both LCSCs and TILs, the relationship between the two has been very marginally considered. We analyzed whether these two cell types may be related as a prerequisite for novel diagnostic and therapeutic approaches.
METHODS METHODS
In this cross-sectional study, NSCLC human surgical specimens from 12 patients were tested by ALDEFLUOR assay to identify ALDH
RESULTS RESULTS
Statistically positive correlations were found between ALDH+ and CD8+, and between ALDH+ and CD3+ cells populations; no correlation was found between ALDH+ and CD4+ cells. The expression of CD3+ and CD8+ by cells accounted for 40.1% and 58.7%, respectively, of the variability of ALDH+ cell expression by an R-squared index, which highlights the strong correlation between TILs and LCSCs. Immunohistochemistry revealed 6-25% positive cells.
CONCLUSIONS CONCLUSIONS
We report a correlation between cytotoxic TILs and LCSCs, which may contribute to the future development of targeted therapies focusing on the different roles of lymphocytes against lung cancer.

Identifiants

pubmed: 31930020
doi: 10.21037/atm.2019.11.27
pii: atm-07-22-619
pmc: PMC6944548
doi:

Types de publication

Journal Article

Langues

eng

Pagination

619

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

2019 Annals of Translational Medicine. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: The authors have no conflicts of interest to declare.

Références

Sci Rep. 2015 Oct 08;5:14896
pubmed: 26447332
J Cancer. 2017 Sep 15;8(16):3190-3197
pubmed: 29158791
Blood. 2009 Feb 19;113(8):1670-80
pubmed: 18971422
Eur J Cancer. 2019 Jan;106:144-159
pubmed: 30528799
Oncotarget. 2016 Feb 9;7(6):7227-40
pubmed: 26811495
Eur J Cardiothorac Surg. 2015 Aug;48(2):180-93
pubmed: 25971435
Stem Cells. 2015 Jul;33(7):2085-92
pubmed: 25873269
BMC Cancer. 2014 Apr 30;14:304
pubmed: 24884875
Cytotherapy. 2007;9(3):259-74
pubmed: 17464758
Mod Pathol. 2011 May;24(5):671-82
pubmed: 21240258
J Immunother Cancer. 2018 Jul 17;6(1):75
pubmed: 30012210
Stem Cells Int. 2016;2016:5603135
pubmed: 26880969
Biomedicine (Taipei). 2017 Dec;7(4):23
pubmed: 29130448
Chin Med J (Engl). 2015 Jan 5;128(1):105-10
pubmed: 25563322
J Thorac Oncol. 2016 Sep;11(9):1433-46
pubmed: 27448762
Biochim Biophys Acta. 2015 Dec;1856(2):189-210
pubmed: 26297204
Cureus. 2018 Sep 4;10(9):e3254
pubmed: 30416904
Nat Prod Res. 2007 Jan;21(1):13-7
pubmed: 17365682
Front Immunol. 2019 Feb 01;9:3101
pubmed: 30774636
Front Immunol. 2017 Sep 13;8:1124
pubmed: 28955340
Cancer Gene Ther. 2017 Feb;24(2):57-63
pubmed: 28084319
Adv Anat Pathol. 2017 Nov;24(6):311-335
pubmed: 28777143
Transl Lung Cancer Res. 2015 Dec;4(6):689-703
pubmed: 26798578
Cancer Res. 2010 Dec 1;70(23):9937-48
pubmed: 21118965
Cancer Immunol Immunother. 2009 Oct;58(10):1535-44
pubmed: 19562338
Cancer Res. 1992 Apr 1;52(7):1770-4
pubmed: 1551107
Cell Stem Cell. 2007 Nov;1(5):555-67
pubmed: 18371393
J Clin Epidemiol. 2008 Apr;61(4):344-9
pubmed: 18313558
Int J Mol Sci. 2019 Jun 08;20(11):null
pubmed: 31181772
Oncol Lett. 2018 Jun;15(6):8187-8194
pubmed: 29805553
Cell Death Differ. 2014 Jan;21(1):5-14
pubmed: 23579243
Intractable Rare Dis Res. 2017 Nov;6(4):234-241
pubmed: 29259850
J Oral Maxillofac Pathol. 2017 Sep-Dec;21(3):463
pubmed: 29391738
Onco Targets Ther. 2014 Jun 23;7:1129-34
pubmed: 25018639
Transl Lung Cancer Res. 2016 Jun;5(3):288-300
pubmed: 27413711

Auteurs

Valentina Masciale (V)

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Giulia Grisendi (G)

Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Federico Banchelli (F)

Center of Statistic, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Roberto D'Amico (R)

Center of Statistic, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Antonino Maiorana (A)

Institute of Pathology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Pamela Sighinolfi (P)

Institute of Pathology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Massimo Pinelli (M)

Division of Plastic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Eleonora Lovati (E)

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Alessandro Stefani (A)

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Uliano Morandi (U)

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Massimo Dominici (M)

Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Beatrice Aramini (B)

Division of Thoracic Surgery, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.

Classifications MeSH