Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients.
Adult
Aged
Aged, 80 and over
Algorithms
Biomarkers, Tumor
/ analysis
Carcinoma, Renal Cell
/ genetics
DNA-Binding Proteins
/ genetics
Decision Support Techniques
Female
Humans
Immunohistochemistry
Immunophenotyping
Kidney Neoplasms
/ genetics
Leukocyte Common Antigens
/ analysis
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Middle Aged
Mutation
Nuclear Proteins
/ genetics
Phenotype
Predictive Value of Tests
Prognosis
T-Lymphocytes
/ immunology
Transcription Factors
/ genetics
Tumor Microenvironment
/ immunology
Tumor Suppressor Proteins
/ genetics
Ubiquitin Thiolesterase
/ genetics
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
ISSN: 1530-0285
Titre abrégé: Mod Pathol
Pays: United States
ID NLM: 8806605
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
14
01
2021
accepted:
18
06
2021
revised:
18
06
2021
pubmed:
4
7
2021
medline:
22
3
2022
entrez:
3
7
2021
Statut:
ppublish
Résumé
While the abundance and phenotype of tumor-infiltrating lymphocytes are linked with clinical survival, their spatial coordination and its clinical significance remain unclear. Here, we investigated the immune profile of intratumoral and peritumoral tissue of clear cell renal cell carcinoma patients (n = 64). We trained a cell classifier to detect lymphocytes from hematoxylin and eosin stained tissue slides. Using unsupervised classification, patients were further classified into immune cold, hot and excluded topographies reflecting lymphocyte abundance and localization. The immune topography distribution was further validated with The Cancer Genome Atlas digital image dataset. We showed association between PBRM1 mutation and immune cold topography, STAG1 mutation and immune hot topography and BAP1 mutation and immune excluded topography. With quantitative multiplex immunohistochemistry we analyzed the expression of 23 lymphocyte markers in intratumoral and peritumoral tissue regions. To study spatial interactions, we developed an algorithm quantifying the proportion of adjacent immune cell pairs and their immunophenotypes. Immune excluded tumors were associated with superior overall survival (HR 0.19, p = 0.02) and less extensive metastasis. Intratumoral T cells were characterized with pronounced expression of immunological activation and exhaustion markers such as granzyme B, PD1, and LAG3. Immune cell interaction occurred most frequently in the intratumoral region and correlated with CD45RO expression. Moreover, high proportion of peritumoral CD45RO+ T cells predicted poor overall survival. In summary, intratumoral and peritumoral tissue regions represent distinct immunospatial profiles and are associated with clinicopathologic characteristics.
Identifiants
pubmed: 34215851
doi: 10.1038/s41379-021-00864-0
pii: S0893-3952(22)00384-2
pmc: PMC8592837
doi:
Substances chimiques
BAP1 protein, human
0
Biomarkers, Tumor
0
DNA-Binding Proteins
0
Nuclear Proteins
0
PBRM1 protein, human
0
STAG1 protein, human
0
Transcription Factors
0
Tumor Suppressor Proteins
0
Leukocyte Common Antigens
EC 3.1.3.48
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2229-2241Informations de copyright
© 2021. The Author(s).
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