Clinical relevance of PD-1 positive CD8 T-cells in gastric cancer.
CD8 T-cells
Gastric cancer
Multiplex immunohistochemistry
PD-1
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
02
06
2022
accepted:
11
01
2023
medline:
21
4
2023
pubmed:
14
2
2023
entrez:
13
2
2023
Statut:
ppublish
Résumé
We evaluated the relevance of PD-1 Discovery cohort: GC samples were evaluated for AE1/3, CD8, PD-1, Ki-67 and Granzyme-B expression with fluorescence-based multiplex immunohistochemistry (mIHC). Validation cohorts: we analyzed bulk RNAseq GC datasets from TCGA, the "3G" chemotherapy trial and an immunotherapy phase 2 trial. The cox proportional hazards model was used to identify factors that influenced overall survival (OS). To study the TME, we analyzed single-cell RNAseq performed on GCs. In the discovery cohort of 350 GCs, increased PD-1 expression of CD8 T-cells was prognostic for OS (HR 0.822, p = 0.042). PD-1 expression in CD8 T-cells highly correlated with cytolytic [Granzyme-B This is one of the largest GC cohorts of mIHC combined with analysis of multiple datasets providing orthogonal validation of the clinical relevance of PD-1
Sections du résumé
BACKGROUND
We evaluated the relevance of PD-1
METHODS
Discovery cohort: GC samples were evaluated for AE1/3, CD8, PD-1, Ki-67 and Granzyme-B expression with fluorescence-based multiplex immunohistochemistry (mIHC). Validation cohorts: we analyzed bulk RNAseq GC datasets from TCGA, the "3G" chemotherapy trial and an immunotherapy phase 2 trial. The cox proportional hazards model was used to identify factors that influenced overall survival (OS). To study the TME, we analyzed single-cell RNAseq performed on GCs.
RESULTS
In the discovery cohort of 350 GCs, increased PD-1 expression of CD8 T-cells was prognostic for OS (HR 0.822, p = 0.042). PD-1 expression in CD8 T-cells highly correlated with cytolytic [Granzyme-B
CONCLUSION
This is one of the largest GC cohorts of mIHC combined with analysis of multiple datasets providing orthogonal validation of the clinical relevance of PD-1
Identifiants
pubmed: 36781556
doi: 10.1007/s10120-023-01364-7
pii: 10.1007/s10120-023-01364-7
pmc: PMC10115710
doi:
Substances chimiques
Programmed Cell Death 1 Receptor
0
Granzymes
EC 3.4.21.-
Ki-67 Antigen
0
B7-H1 Antigen
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
393-404Subventions
Organisme : National Medical Research Council Singapore
ID : OFLCG18May-0023
Organisme : National Medical Research Council Singapore
ID : CGAug16M005
Informations de copyright
© 2023. The Author(s).
Références
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians.n/a(n/a).
Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet (London, England). 2017;390(10111):2461–71.
pubmed: 28993052
doi: 10.1016/S0140-6736(17)31827-5
Shitara K, Van Cutsem E, Bang Y-J, Fuchs C, Wyrwicz L, Lee K-W, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial. JAMA Oncol. 2020;6(10):1571–80.
pubmed: 32880601
doi: 10.1001/jamaoncol.2020.3370
Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandalà M, Ryu MH, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet (London, England). 2018;392(10142):123–33.
pubmed: 29880231
doi: 10.1016/S0140-6736(18)31257-1
Zhao JJ, Yap DWT, Chan YH, Tan BKJ, Teo CB, Syn NL, et al. Low Programmed death-ligand 1-expressing subgroup outcomes of first-line immune checkpoint inhibitors in gastric or esophageal adenocarcinoma. J Clin Oncol: Off J Am Soc Clin Oncol. 2022;40(4):392–402.
doi: 10.1200/JCO.21.01862
Sundar R, Smyth EC, Peng S, Yeong JPS, Tan P. Predictive biomarkers of immune checkpoint inhibition in gastroesophageal cancers. Front Oncol. 2020;10:763.
pubmed: 32500029
pmcid: 7243739
doi: 10.3389/fonc.2020.00763
Moehler M, Shitara K, Garrido M, Salman P, Shen L, Wyrwicz L, et al. LBA6_PR Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): first results of the checkmate 649 study. Ann Oncol. 2020;31:S1191.
doi: 10.1016/j.annonc.2020.08.2296
Park Y, Koh J, Na HY, Kwak Y, Lee KW, Ahn SH, et al. PD-L1 testing in gastric cancer by the combined positive score of the 22C3 PharmDx and SP263 assay with clinically relevant cut-offs. Cancer Res Treat. 2020;52(3):661–70.
pubmed: 32019283
pmcid: 7373862
doi: 10.4143/crt.2019.718
Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, et al. PD-L1 and gastric cancer prognosis: a systematic review and meta-analysis. PLoS ONE. 2017;12(8): e0182692.
pubmed: 28796808
pmcid: 5552131
doi: 10.1371/journal.pone.0182692
Zhang M, Dong Y, Liu H, Wang Y, Zhao S, Xuan Q, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1901 patients. Sci Rep. 2016;6(1):37933.
pubmed: 27892511
pmcid: 5124943
doi: 10.1038/srep37933
Mittal D, Gubin MM, Schreiber RD, Smyth MJ. New insights into cancer immunoediting and its three component phases–elimination, equilibrium and escape. Curr Opin Immunol. 2014;27:16–25.
pubmed: 24531241
pmcid: 4388310
doi: 10.1016/j.coi.2014.01.004
Kansy BA, Concha-Benavente F, Srivastava RM, Jie H-B, Shayan G, Lei Y, et al. PD-1 status in CD8(+) T cells associates with survival and Anti-PD-1 therapeutic outcomes in head and neck cancer. Can Res. 2017;77(22):6353–64.
doi: 10.1158/0008-5472.CAN-16-3167
Diana A, Wang LM, D’Costa Z, Allen P, Azad A, Silva MA, et al. Prognostic value, localization and correlation of PD-1/PD-L1, CD8 and FOXP3 with the desmoplastic stroma in pancreatic ductal adenocarcinoma. Oncotarget. 2016;7(27):40992–1004.
pubmed: 27329602
pmcid: 5173037
doi: 10.18632/oncotarget.10038
Yeong J, Lim JCT, Lee B, Li H, Ong CCH, Thike AA, et al. Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer. J Immunother Cancer. 2019;7(1):34.
pubmed: 30728081
pmcid: 6366051
doi: 10.1186/s40425-019-0499-y
Halse H, Colebatch AJ, Petrone P, Henderson MA, Mills JK, Snow H, et al. Multiplex immunohistochemistry accurately defines the immune context of metastatic melanoma. Sci Rep. 2018;8(1):11158.
pubmed: 30042403
pmcid: 6057961
doi: 10.1038/s41598-018-28944-3
Gorris MAJ, Halilovic A, Rabold K, van Duffelen A, Wickramasinghe IN, Verweij D, et al. Eight-color multiplex immunohistochemistry for simultaneous detection of multiple immune checkpoint molecules within the tumor microenvironment. J Immunol. 2018;200(1):347–54.
pubmed: 29141863
doi: 10.4049/jimmunol.1701262
Yeong J, Tan T, Chow ZL, Cheng Q, Lee B, Seet A, et al. Multiplex immunohistochemistry/immunofluorescence (mIHC/IF) for PD-L1 testing in triple-negative breast cancer: a translational assay compared with conventional IHC. J Clin Pathol. 2020;73(9):557–62.
pubmed: 31969377
doi: 10.1136/jclinpath-2019-206252
Deng M, Brägelmann J, Kryukov I, Saraiva-Agostinho N, Perner S. FirebrowseR: an R client to the broad institute’s firehose pipeline. Database (Oxford). 2017;2017:baw160.
pubmed: 28062517
pmcid: 5216271
doi: 10.1093/database/baw160
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, et al. The immune landscape of cancer. Immunity. 2018;48(4):812-30.e14.
pubmed: 29628290
pmcid: 5982584
doi: 10.1016/j.immuni.2018.03.023
Sundar R, Huang KK, Qamra A, Kim KM, Kim ST, Kang WK, et al. Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer. Ann Oncology: Off J Eur Soc Med Oncol. 2019;30(3):424–30.
doi: 10.1093/annonc/mdy550
Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018;24(9):1449–58.
pubmed: 30013197
doi: 10.1038/s41591-018-0101-z
An O, Song Y, Ke X, So JB, Sundar R, Yang H, et al. “3G” trial: an RNA editing signature to guide gastric cancer chemotherapy. Cancer Res. 2021;81(10):2788–98.
pubmed: 33558338
doi: 10.1158/0008-5472.CAN-20-2872
Kumar V, Ramnarayanan K, Sundar R, Padmanabhan N, Srivastava S, Koiwa M, et al. Single-cell atlas of lineage states, tumor microenvironment, and subtype-specific expression programs in gastric cancer. Cancer Discov. 2022;12(3):670–91.
pubmed: 34642171
pmcid: 9394383
doi: 10.1158/2159-8290.CD-21-0683
Yong WP, Rha SY, Tan IB, Choo SP, Syn NL, Koh V, et al. Real-time tumor gene expression profiling to direct gastric cancer chemotherapy: proof-of-concept “3G” trial. Clin Cancer Res: Off J Am Assoc Cancer Res. 2018;24(21):5272–81.
doi: 10.1158/1078-0432.CCR-18-0193
Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9.
doi: 10.1038/nature13480
Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res. 2013;73(1):128–38.
pubmed: 23135914
doi: 10.1158/0008-5472.CAN-12-2606
Gehring AJ, Ho ZZ, Tan AT, Aung MO, Lee KH, Tan KC, et al. Profile of tumor antigen-specific CD8 T cells in patients with hepatitis B virus-related hepatocellular carcinoma. Gastroenterology. 2009;137(2):682–90.
pubmed: 19394336
doi: 10.1053/j.gastro.2009.04.045
Oudejans JJ, Harijadi H, Kummer JA, Tan IB, Bloemena E, Middeldorp JM, et al. High numbers of granzyme B/CD8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent. J Pathol. 2002;198(4):468–75.
pubmed: 12434416
doi: 10.1002/path.1236
Nakano O, Sato M, Naito Y, Suzuki K, Orikasa S, Aizawa M, et al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res. 2001;61(13):5132–6.
pubmed: 11431351
van Houdt IS, Sluijter BJ, van Leeuwen PA, Moesbergen LM, Hooijberg E, Meijer CJ, et al. Absence of Granzyme B positive tumour-infiltrating lymphocytes in primary melanoma excisional biopsies is strongly associated with the presence of sentinel lymph node metastasis. Cell Oncol: Off J Int Soc Cell Oncol. 2009;31(5):407–13.
Ferlazzo G, Münz C. NK cell compartments and their activation by dendritic cells. J Immunol. 2004;172(3):1333.
pubmed: 14734707
doi: 10.4049/jimmunol.172.3.1333
Zaravinos A, Roufas C, Nagara M, de Lucas MB, Oblovatskaya M, Efstathiades C, et al. Cytolytic activity correlates with the mutational burden and deregulated expression of immune checkpoints in colorectal cancer. J Exp Clin Cancer Res. 2019;38(1):364.
pubmed: 31429779
pmcid: 6701076
doi: 10.1186/s13046-019-1372-z
Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutiérrez E, et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med. 2022;386(1):24–34.
pubmed: 34986285
pmcid: 9844513
doi: 10.1056/NEJMoa2109970
Park Y, Seo AN, Koh J, Nam SK, Kwak Y, Ahn SH, et al. Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry. Oncoimmunology. 2021;10(1):1954761.
pubmed: 34367732
pmcid: 8312618
doi: 10.1080/2162402X.2021.1954761
Däster S, Eppenberger-Castori S, Mele V, Schäfer HM, Schmid L, Weixler B, et al. Low expression of programmed death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T lymphocyte infiltration identify a subgroup of patients with gastric and esophageal adenocarcinoma with severe prognosis. Front Med. 2020;7:144.
doi: 10.3389/fmed.2020.00144
Yu K, Gu Y, Zhang P, Fang H, Cao Y, Wang J, et al. Intratumoral PD-1(+)CD8(+) T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer. Br J Cancer. 2022;127:1709–17.
pubmed: 36002752
pmcid: 9596411
doi: 10.1038/s41416-022-01939-8
Saito H, Shimizu S, Kono Y, Murakami Y, Shishido Y, Miyatani K, et al. PD-1 expression on circulating CD8(+) T-cells as a prognostic marker for patients with gastric cancer. Anticancer Res. 2019;39(1):443–8.
pubmed: 30591493
doi: 10.21873/anticanres.13132
Shen Y, Teng Y, Lv Y, Zhao Y, Qiu Y, Chen W, et al. PD-1 does not mark tumor-infiltrating CD8+ T cell dysfunction in human gastric cancer. J Immunother Cancer. 2020;8(2): e000422.
pubmed: 32753468
pmcid: 7406116
doi: 10.1136/jitc-2019-000422
Ito S, Masuda T, Noda M, Hu Q, Shimizu D, Kuroda Y, et al. Prognostic significance of PD-1, PD-L1 and CD8 gene expression levels in gastric cancer. Oncology. 2020;98(7):501–11.
pubmed: 32380498
doi: 10.1159/000506075
Lee K, Hwang H, Nam KT. Immune response and the tumor microenvironment: how they communicate to regulate gastric cancer. Gut and liver. 2014;8(2):131–9.
pubmed: 24672653
pmcid: 3964262
doi: 10.5009/gnl.2014.8.2.131
de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37.
pubmed: 16397525
doi: 10.1038/nrc1782
Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf Anna C, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39(4):782–95.
pubmed: 24138885
doi: 10.1016/j.immuni.2013.10.003
Lee HE, Chae SW, Lee YJ, Kim MA, Lee HS, Lee BL, et al. Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer. Br J Cancer. 2008;99(10):1704–11.
pubmed: 18941457
pmcid: 2584941
doi: 10.1038/sj.bjc.6604738
Lee JS, Won HS, Sun DS, Hong JH, Ko YH. Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2018;97(32): e11769.
pubmed: 30095632
doi: 10.1097/MD.0000000000011769
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102(51):18538–43.
pubmed: 16344461
pmcid: 1311741
doi: 10.1073/pnas.0509182102
Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol: Off J Am Soc Clin Oncol. 2011;29(15):1949–55.
doi: 10.1200/JCO.2010.30.5037
Idos GE, Kwok J, Bonthala N, Kysh L, Gruber SB, Qu C. The prognostic implications of tumor infiltrating lymphocytes in colorectal cancer: a systematic review and meta-analysis. Sci Rep. 2020;10(1):3360.
pubmed: 32099066
pmcid: 7042281
doi: 10.1038/s41598-020-60255-4