Expression patterns of novel immunotherapy targets in intermediate- and high-grade lung neuroendocrine neoplasms.
Humans
Lung Neoplasms
/ immunology
Male
Female
Hepatitis A Virus Cellular Receptor 2
/ metabolism
Immunotherapy
/ methods
Neuroendocrine Tumors
/ immunology
Middle Aged
Aged
Glucocorticoid-Induced TNFR-Related Protein
/ metabolism
Biomarkers, Tumor
/ metabolism
B7 Antigens
/ metabolism
Adult
Neoplasm Grading
OX40 Ligand
/ metabolism
Prognosis
Aged, 80 and over
Immune phenotype
Immunohistochemistry
Immunotherapy target
Lung neuroendocrine neoplasm
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
06
11
2023
accepted:
14
04
2024
medline:
2
5
2024
pubmed:
2
5
2024
entrez:
1
5
2024
Statut:
epublish
Résumé
Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs. The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored. Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively). LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.
Sections du résumé
BACKGROUND
BACKGROUND
Advancements in immunotherapeutic approaches only had a modest impact on the therapy of lung neuroendocrine neoplasms (LNENs). Our multicenter study aimed to investigate the expression patterns of novel immunotherapy targets in intermediate- and high-grade LNENs.
METHODS
METHODS
The expressions of V-domain Ig suppressor of T cell activation (VISTA), OX40L, Glucocorticoid-induced TNF receptor (GITR), and T cell immunoglobulin and mucin domain 3 (TIM3) proteins were measured by immunohistochemistry in surgically resected tumor samples of 26 atypical carcinoid (AC), 49 large cell neuroendocrine lung cancer (LCNEC), and 66 small cell lung cancer (SCLC) patients. Tumor and immune cells were separately scored.
RESULTS
RESULTS
Tumor cell TIM3 expression was the highest in ACs (p < 0.001), whereas elevated tumor cell GITR levels were characteristic for both ACs and SCLCs (p < 0.001 and p = 0.011, respectively). OX40L expression of tumor cells was considerably lower in ACs (vs. SCLCs; p < 0.001). Tumor cell VISTA expression was consistently low in LNENs, with no significant differences across histological subtypes. ACs were the least immunogenic tumors concerning immune cell abundance (p < 0.001). Immune cell VISTA and GITR expressions were also significantly lower in these intermediate-grade malignancies than in SCLCs or in LCNECs. Immune cell TIM3 and GITR expressions were associated with borderline prognostic significance in our multivariate model (p = 0.057 and p = 0.071, respectively).
CONCLUSIONS
CONCLUSIONS
LNEN subtypes have characteristic and widely divergent VISTA, OX40L, GITR, and TIM3 protein expressions. By shedding light on the different expression patterns of these immunotherapy targets, the current multicenter study provides support for the future implementation of novel immunotherapeutic approaches.
Identifiants
pubmed: 38693435
doi: 10.1007/s00262-024-03704-7
pii: 10.1007/s00262-024-03704-7
doi:
Substances chimiques
Hepatitis A Virus Cellular Receptor 2
0
HAVCR2 protein, human
0
Glucocorticoid-Induced TNFR-Related Protein
0
Biomarkers, Tumor
0
B7 Antigens
0
VSIR protein, human
0
OX40 Ligand
0
TNFRSF18 protein, human
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
114Subventions
Organisme : Nemzeti Kutatási Fejlesztési és Innovációs Hivatal
ID : TKP2021-EGA-33
Organisme : Semmelweis Egyetem
ID : Semmelweis 250+ Excellence PhD Scholarship
Organisme : Austrian Science Fund
ID : FWF No. T 1062-B33
Organisme : Austrian Science Fund
ID : FWF I3522
Organisme : Hochschuljubiläumsstiftung der Stadt Wien
ID : Innovative Interdisciplinary Cancer Research
Organisme : Magyar Tudományos Akadémia
ID : PC2022-II-19/1/2022
Organisme : Magyar Tudományos Akadémia
ID : Bolyai Research Scholarship
Organisme : Innovációs és Technológiai Minisztérium
ID : UNKP-20-3
Organisme : International Association for the Study of Lung Cancer
ID : International Lung Cancer Foundation Young Investigator Grant (2022)
Informations de copyright
© 2024. The Author(s).
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