Multi-Parameter Quantitative Imaging of Tumor Microenvironments Reveals Perivascular Immune Niches Associated With Anti-Tumor Immunity.
Animals
Antibodies, Bispecific
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
B7-H1 Antigen
/ antagonists & inhibitors
Carcinoembryonic Antigen
/ genetics
Cell Line, Tumor
Dendritic Cells
/ immunology
Immune Checkpoint Inhibitors
/ therapeutic use
Macrophages
/ immunology
Male
Mice, Inbred BALB C
Mice, Transgenic
Microscopy, Confocal
Neoplasms
/ diagnostic imaging
T-Lymphocytes
/ immunology
Tumor Microenvironment
/ immunology
CD8 T cells
blood vessels
checkpoint blockade therapy
dendritic cells
macrophages
quantitative microscopy
spatial analysis
tumor microenvironments
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
06
2021
accepted:
14
07
2021
entrez:
23
8
2021
pubmed:
24
8
2021
medline:
27
11
2021
Statut:
epublish
Résumé
Tumors are populated by a multitude of immune cell types with varied phenotypic and functional properties, which can either promote or inhibit anti-tumor responses. Appropriate localization and function of these cells within tumors is critical for protective immunity, with CD8 T cell infiltration being a biomarker of disease outcome and therapeutic efficacy. Recent multiplexed imaging approaches have revealed highly complex patterns of localization for these immune cell subsets and the generation of distinct tumor microenvironments (TMEs), which can vary among cancer types, individuals, and within individual tumors. While it is recognized that TMEs play a pivotal role in disease progression, a better understanding of their composition, organization, and heterogeneity, as well as how distinct TMEs are reshaped with immunotherapy, is necessary. Here, we performed spatial analysis using multi-parameter confocal imaging, histocytometry, and CytoMAP to study the microanatomical organization of immune cells in two widely used preclinical cancer models, the MC38 colorectal and KPC pancreatic murine tumors engineered to express human carcinoembryonic antigen (CEA). Immune responses were examined in either unperturbed tumors or after immunotherapy with a CEA T cell bispecific (CEA-TCB) surrogate antibody and anti-PD-L1 treatment. CEA-TCB mono and combination immunotherapy markedly enhanced intra-tumoral cellularity of CD8 T cells, dominantly driven by the expansion of TCF1
Identifiants
pubmed: 34421928
doi: 10.3389/fimmu.2021.726492
pmc: PMC8375665
doi:
Substances chimiques
Antibodies, Bispecific
0
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
Carcinoembryonic Antigen
0
Cd274 protein, mouse
0
Immune Checkpoint Inhibitors
0
cibisatamab
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
726492Subventions
Organisme : NIAID NIH HHS
ID : R21 AI142667
Pays : United States
Informations de copyright
Copyright © 2021 Stoltzfus, Sivakumar, Kunz, Olin Pope, Menietti, Speziale, Adelfio, Bacac, Colombetti, Perro and Gerner.
Déclaration de conflit d'intérêts
MP, LK, EM, SC, DS, RA and MB were employees of Roche at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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