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CTLA-4 Immunohistochemistry and Quantitative Image Analysis for Profiling of Human Cancers.


ABSTRACT: There is an important need in immuno-oncology to develop reliable immunohistochemistry (IHC) to assess the expression of CTLA-4+ tumor-infiltrating lymphocytes in human cancers and quantify them with image analysis (IA). We used commercial polyclonal and monoclonal antibodies and characterized three chromogenic cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) assays with suitable specificity and sensitivity for use in formalin-fixed, paraffin-embedded (FFPE) tissues. We found variable numbers of CTLA-4+ lymphocytes in multiple types of cancer and secondary lymphoid organs (SLOs) and other normal human tissues. Combining CTLA-4 with CD3, CD4, or CD8 by immunofluorescence showed that CTLA-4+ lymphocytes in SLOs and tumors were typically CD3+ and CD4+, but not CD8+. Individual lymphocytes expressed CTLA-4 either as primarily granular cytoplasmic staining or as excentric globular deposits. The CTLA-4/FoxP3 (forkhead box P3 protein) duplex IHC demonstrated that CTLA-4+/FoxP3- lymphocytes predominated in the germinal centers of SLOs and tumor tertiary lymphoid structures (TLSs), whereas CTLA-4+/FoxP3+ lymphocytes populated the T-cell zone of SLOs and TLSs, plus tumor stroma. IA scoring was highly comparable with pathologist scoring for CTLA-4 and CTLA-4/FoxP3 assays and a FoxP3 single IHC. Our findings show that CTLA-4 IHC can be used to reliably label lymphocytes in FFPE human tissues, making it possible to investigate the role of CTLA-4 in the tumor microenvironment.

SUBMITTER: Brown C 

PROVIDER: S-EPMC6882065 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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CTLA-4 Immunohistochemistry and Quantitative Image Analysis for Profiling of Human Cancers.

Brown Charles C   Sekhavati Farzad F   Cardenes Ruben R   Windmueller Claudia C   Dacosta Karma K   Rodriguez-Canales Jaime J   Steele Keith E KE  

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20191014 12


There is an important need in immuno-oncology to develop reliable immunohistochemistry (IHC) to assess the expression of CTLA-4<sup>+</sup> tumor-infiltrating lymphocytes in human cancers and quantify them with image analysis (IA). We used commercial polyclonal and monoclonal antibodies and characterized three chromogenic cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) assays with suitable specificity and sensitivity for use in formalin-fixed, paraffin-embedded (FFPE) tissues. We found vari  ...[more]

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