Tumor and immune remodeling following radiotherapy in human renal cell carcinoma.
Immunomodulation
Kidney Neoplasms
Lymphocytes, Tumor-Infiltrating
Radiotherapy
Tumor Microenvironment
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
accepted:
03
04
2023
medline:
24
4
2023
pubmed:
21
4
2023
entrez:
20
04
2023
Statut:
ppublish
Résumé
Studies evaluating peripheral patient samples show radiation can modulate immune responses, yet the biological changes in human tumors particularly at the cellular level remain largely unknown. Here, we address how radiation treatment shapes the immune compartment and interactions with cancer cells within renal cell carcinoma (RCC) patient tumors. To identify how radiation shaped the immune compartment and potential immune interactions with tumor cells we evaluated RCC tumors from patients treated only with nephrectomy or with radiation followed by nephrectomy. Spectral flow cytometry using a 35-marker panel was performed on cell suspensions to evaluate protein expression within immune subsets. To reveal how radiation alters programming of immune populations and interactions with tumor cells, we examined transcriptional changes by single-cell RNA sequencing (scRNAseq). Spectral flow cytometry analysis revealed increased levels of early-activated as well as effector programmed cell death protein-1 (PD-1) These findings identify the source of IFN enrichment within irradiated RCC and reveal heightened levels of PD-1
Sections du résumé
BACKGROUND
Studies evaluating peripheral patient samples show radiation can modulate immune responses, yet the biological changes in human tumors particularly at the cellular level remain largely unknown. Here, we address how radiation treatment shapes the immune compartment and interactions with cancer cells within renal cell carcinoma (RCC) patient tumors.
METHODS
To identify how radiation shaped the immune compartment and potential immune interactions with tumor cells we evaluated RCC tumors from patients treated only with nephrectomy or with radiation followed by nephrectomy. Spectral flow cytometry using a 35-marker panel was performed on cell suspensions to evaluate protein expression within immune subsets. To reveal how radiation alters programming of immune populations and interactions with tumor cells, we examined transcriptional changes by single-cell RNA sequencing (scRNAseq).
RESULTS
Spectral flow cytometry analysis revealed increased levels of early-activated as well as effector programmed cell death protein-1 (PD-1)
CONCLUSIONS
These findings identify the source of IFN enrichment within irradiated RCC and reveal heightened levels of PD-1
Identifiants
pubmed: 37080610
pii: jitc-2022-006392
doi: 10.1136/jitc-2022-006392
pmc: PMC10124322
pii:
doi:
Substances chimiques
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001412
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016056
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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