Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients

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dc.contributor.author Bruck, Oscar
dc.contributor.author Lee, Moon Hee
dc.contributor.author Turkki, Riku
dc.contributor.author Uski, Ilona
dc.contributor.author Penttilä, Patrick
dc.contributor.author Paavolainen, Lassi
dc.contributor.author Kovanen, Panu
dc.contributor.author Järvinen, Petrus
dc.contributor.author Bono, Petri
dc.contributor.author Pellinen, Teijo
dc.contributor.author Mustjoki, Satu
dc.contributor.author Kreutzman, Anna
dc.date.accessioned 2022-02-16T17:33:03Z
dc.date.available 2022-02-16T17:33:03Z
dc.date.issued 2021-12
dc.identifier.citation Bruck , O , Lee , M H , Turkki , R , Uski , I , Penttilä , P , Paavolainen , L , Kovanen , P , Järvinen , P , Bono , P , Pellinen , T , Mustjoki , S & Kreutzman , A 2021 , ' Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients ' , Modern Pathology , vol. 34 , no. 12 , pp. 2229-2241 . https://doi.org/10.1038/s41379-021-00864-0
dc.identifier.other PURE: 168060991
dc.identifier.other PURE UUID: 37adfe20-72b2-448b-81e6-8151b45525e9
dc.identifier.other WOS: 000669171200001
dc.identifier.other ORCID: /0000-0002-8690-6983/work/108463524
dc.identifier.other ORCID: /0000-0002-3778-0237/work/108466253
dc.identifier.other ORCID: /0000-0003-1508-2718/work/108466539
dc.identifier.other ORCID: /0000-0002-0816-8241/work/108466652
dc.identifier.uri http://hdl.handle.net/10138/340487
dc.description.abstract 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. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Modern Pathology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject UP-REGULATION
dc.subject EXPRESSION
dc.subject BLOCKADE
dc.subject 3111 Biomedicine
dc.title Spatial immunoprofiling of the intratumoral and peritumoral tissue of renal cell carcinoma patients en
dc.type Article
dc.contributor.organization TRIMM - Translational Immunology Research Program
dc.contributor.organization Research Programs Unit
dc.contributor.organization Digital Precision Cancer Medicine (iCAN)
dc.contributor.organization HUS Comprehensive Cancer Center
dc.contributor.organization Department of Oncology
dc.contributor.organization Hematologian yksikkö
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.contributor.organization Urologian yksikkö
dc.contributor.organization HUS Abdominal Center
dc.contributor.organization HUSLAB
dc.contributor.organization Department of Pathology
dc.contributor.organization Medicum
dc.contributor.organization University of Helsinki
dc.contributor.organization Clinicum
dc.contributor.organization Department of Surgery
dc.contributor.organization Heikki Joensuu / Principal Investigator
dc.contributor.organization Precision Systems Medicine
dc.contributor.organization Department of Clinical Chemistry and Hematology
dc.contributor.organization Bioimage Profiling
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41379-021-00864-0
dc.relation.issn 0893-3952
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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