High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma.
Humans
Esophageal Neoplasms
/ immunology
Programmed Cell Death 1 Receptor
/ metabolism
Adenocarcinoma
/ immunology
Lymphocytes, Tumor-Infiltrating
/ immunology
Apyrase
/ metabolism
CD8-Positive T-Lymphocytes
/ immunology
Male
Female
Antigens, CD
/ metabolism
Middle Aged
Aged
Prognosis
Biomarkers, Tumor
Integrin alpha Chains
/ metabolism
Adenocarcinoma
CD8+ Lymphocyte
Neoadjuvant therapy
Oesophageal cancer
Tissue resident memory cell
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
05 Sep 2024
05 Sep 2024
Historique:
received:
05
04
2024
accepted:
01
08
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
5
9
2024
Statut:
epublish
Résumé
To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy. Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed. A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity. Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.
Identifiants
pubmed: 39235606
doi: 10.1007/s00262-024-03799-y
pii: 10.1007/s00262-024-03799-y
doi:
Substances chimiques
Programmed Cell Death 1 Receptor
0
Apyrase
EC 3.6.1.5
Antigens, CD
0
PDCD1 protein, human
0
ENTPD1 protein, human
EC 3.6.1.5
Biomarkers, Tumor
0
CD39 antigen
EC 3.6.1.5
Integrin alpha Chains
0
alpha E integrins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
213Subventions
Organisme : Cancer Research UK
ID : A28808
Pays : United Kingdom
Organisme : Royal College of Surgeons of England
ID : A23924
Informations de copyright
© 2024. The Author(s).
Références
Booth ME, Smyth EC (2022) Immunotherapy in Gastro-oesophageal cancer: current practice and the future of personalised therapy. BioDrugs 36(4):473–485
doi: 10.1007/s40259-022-00527-9
pubmed: 35384619
Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S et al (2019) Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 393(10184):1948–1957
doi: 10.1016/S0140-6736(18)32557-1
pubmed: 30982686
Shapiro J, van Lanschot JJB, Hulshof M, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL et al (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098
doi: 10.1016/S1470-2045(15)00040-6
pubmed: 26254683
Noble F, Mellows T, McCormick Matthews LH, Bateman AC, Harris S, Underwood TJ et al (2016) Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma. Cancer Immunol Immunother 65(6):651–662
doi: 10.1007/s00262-016-1826-5
pubmed: 27020682
pmcid: 4880639
Edwards J, Wilmott JS, Madore J, Gide TN, Quek C, Tasker A et al (2018) CD103(+) tumor-resident CD8(+) T cells are associated with improved survival in immunotherapy-naive melanoma patients and expand significantly during anti-PD-1 treatment. Clin Cancer Res 24(13):3036–3045
doi: 10.1158/1078-0432.CCR-17-2257
pubmed: 29599411
Clarke J, Panwar B, Madrigal A, Singh D, Gujar R, Wood O et al (2019) Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer. J Exp Med 216(9):2128–2149
doi: 10.1084/jem.20190249
pubmed: 31227543
pmcid: 6719422
Ganesan AP, Clarke J, Wood O, Garrido-Martin EM, Chee SJ, Mellows T et al (2017) Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nat Immunol 18(8):940–950
doi: 10.1038/ni.3775
pubmed: 28628092
pmcid: 6036910
Kumar BV, Ma W, Miron M, Granot T, Guyer RS, Carpenter DJ et al (2017) Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep 20(12):2921–2934
doi: 10.1016/j.celrep.2017.08.078
pubmed: 28930685
pmcid: 5646692
Steinert EM, Schenkel JM, Fraser KA, Beura LK, Manlove LS, Igyarto BZ et al (2015) Quantifying memory CD8 T cells reveals regionalization of immunosurveillance. Cell 161(4):737–749
doi: 10.1016/j.cell.2015.03.031
pubmed: 25957682
pmcid: 4426972
Duhen T, Duhen R, Montler R, Moses J, Moudgil T, de Miranda NF et al (2018) Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat Commun 9(1):2724
doi: 10.1038/s41467-018-05072-0
pubmed: 30006565
pmcid: 6045647
Waise S, Parker R, Rose-Zerilli MJJ, Layfield DM, Wood O, West J et al (2019) An optimized method to isolate human fibroblasts from tissue for ex vivo analysis. Bio Protoc 9(23):e3440
doi: 10.21769/BioProtoc.3440
pubmed: 33654935
pmcid: 7853986
Picelli S, Faridani OR, Bjorklund AK, Winberg G, Sagasser S, Sandberg R (2014) Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc 9(1):171–181
doi: 10.1038/nprot.2014.006
pubmed: 24385147
Thommen DS, Koelzer VH, Herzig P, Roller A, Trefny M, Dimeloe S et al (2018) A transcriptionally and functionally distinct PD-1(+) CD8(+) T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat Med 24(7):994–1004
doi: 10.1038/s41591-018-0057-z
pubmed: 29892065
pmcid: 6110381
van der Leun AM, Thommen DS, Schumacher TN (2020) CD8(+) T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer 20(4):218–232
doi: 10.1038/s41568-019-0235-4
pubmed: 32024970
pmcid: 7115982
Doering TA, Crawford A, Angelosanto JM, Paley MA, Ziegler CG, Wherry EJ (2012) Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory. Immunity 37(6):1130–1144
doi: 10.1016/j.immuni.2012.08.021
pubmed: 23159438
pmcid: 3749234
Goldrath AW, Luckey CJ, Park R, Benoist C, Mathis D (2004) The molecular program induced in T cells undergoing homeostatic proliferation. Proc Natl Acad Sci U S A 101(48):16885–16890
doi: 10.1073/pnas.0407417101
pubmed: 15548615
pmcid: 534746
Tallon de Lara P, Castanon H, Vermeer M, Nunez N, Silina K, Sobottka B et al (2021) CD39(+)PD-1(+)CD8(+) T cells mediate metastatic dormancy in breast cancer. Nat Commun 12(1):769
doi: 10.1038/s41467-021-21045-2
pubmed: 33536445
pmcid: 7859213
Savas P, Virassamy B, Ye C, Salim A, Mintoff CP, Caramia F et al (2018) Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. Nat Med 24(7):986–993
doi: 10.1038/s41591-018-0078-7
pubmed: 29942092
Simoni Y, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW et al (2018) Bystander CD8(+) T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557(7706):575–579
doi: 10.1038/s41586-018-0130-2
pubmed: 29769722
Thompson EA, Darrah PA, Foulds KE, Hoffer E, Caffrey-Carr A, Norenstedt S et al (2019) Monocytes acquire the ability to prime tissue-resident T cells via IL-10-mediated TGF-beta release. Cell Rep 28(5):1127–1135
doi: 10.1016/j.celrep.2019.06.087
pubmed: 31365858
pmcid: 6825402
Verschoor YL, van de Haar J, van den Berg JG, van Sandick JW, Kodach LL, van Dieren JM et al (2024) Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial. Nat Med 30(2):519–530
doi: 10.1038/s41591-023-02758-x
pubmed: 38191613
pmcid: 10878980