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Tytuł pozycji:

Tumor Lipids of Pediatric Papillary Renal Cell Carcinoma Stimulate Unconventional T Cells

Tytuł:
Tumor Lipids of Pediatric Papillary Renal Cell Carcinoma Stimulate Unconventional T Cells
Autorzy:
Nadine Lehmann
Claudia Paret
Khalifa El Malki
Alexandra Russo
Marie Astrid Neu
Arthur Wingerter
Larissa Seidmann
Sebastian Foersch
Nicole Ziegler
Lea Roth
Nora Backes
Roger Sandhoff
Joerg Faber
Temat:
pediatric papillary renal cell carcinoma
TILs
unconventional T cells
CD1d
lipid antigens
Immunologic diseases. Allergy
RC581-607
Źródło:
Frontiers in Immunology, Vol 11 (2020)
Wydawca:
Frontiers Media S.A., 2020.
Rok publikacji:
2020
Kolekcja:
LCC:Immunologic diseases. Allergy
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1664-3224
Relacje:
https://www.frontiersin.org/article/10.3389/fimmu.2020.01819/full; https://doaj.org/toc/1664-3224
DOI:
10.3389/fimmu.2020.01819
Dostęp URL:
https://doaj.org/article/e138c3c0e30c4a50b0b943bb2fc60865  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.138c3c0e30c4a50b0b943bb2fc60865
Czasopismo naukowe
Papillary renal cell carcinoma (PRCC) is a rare entity in children with no established therapy protocols for advanced diseases. Immunotherapy is emerging as an important therapeutic tool for childhood cancer. Tumor cells can be recognized and killed by conventional and unconventional T cells. Unconventional T cells are able to recognize lipid antigens presented via CD1 molecules independently from major histocompatibility complex, which offers new alternatives for cancer immunotherapies. The nature of those lipids is largely unknown and α-galactosylceramide is currently used as a synthetic model antigen. In this work, we analyzed infiltrating lymphocytes of two pediatric PRCCs using flow cytometry, immunohistochemistry and qRT-PCR. Moreover, we analyzed the CD1d expression within both tumors. Tumor lipids of PRCC samples and three normal kidney samples were fractionated and the recognition of tumor own lipid fractions by unconventional T cells was analyzed in an in vitro assay. We identified infiltrating lymphocytes including γδ T cells and iNKT cells, as well as CD1d expression in both samples. One lipid fraction, containing ceramides and monoacylglycerides amongst others, was able to induce the proliferation of iNKT cells isolated from peripheral blood mononuclear cells (PBMCs) of healthy donors and of one matched PRCC patient. Furthermore, CD1d tetramer stainings revealed that a subset of iNKT cells is able to bind lipids being present in fraction 2 via CD1d. We conclude that PRCCs are infiltrated by conventional and unconventional T cells and express CD1d. Moreover, certain lipids, present in pediatric PRCC, are able to stimulate unconventional T cells. Manipulating these lipids and T cells may open new strategies for therapy of pediatric PRCCs.

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