Universität zu Köln

Mueller, Linda, Kschischo, Maik, Vokuhl, Christian, Stahl, David and Guetgemann, Ines (2022). Stemness Correlates Inversely with MHC Class I Expression in Pediatric Small Round Blue Cell Tumors. Cancers, 14 (15). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Tumors occurring at a young age are distinct from tumors in older individuals, clinically and pathologically. As small round blue cell tumors (SRBCTs), they often show a resemblance to stem cells and immature precursor cells during embryonal development. Recently, immunotherapy has become an option for a subset of patients with limited success. We observed that in almost all the pediatric SRBCT types investigated (n = 1134) there was an inverse relationship, when comparing genes highly expressed in stem cells with genes encoding MHC class I molecules. MHC class I molecules are important in tumor cell recognition by cytotoxic T cells. We suspect that these tumors are derived from multipotent precursor cells that naturally show a low MHC class I expression and a lack of immune recognition necessary for prenatal proliferation and development. Recently, immunotherapeutic approaches have become a feasible option for a subset of pediatric cancer patients. Low MHC class I expression hampers the use of immunotherapies relying on antigen presentation. A well-established stemness score (mRNAsi) was determined using the bulk transcriptomes of 1134 pediatric small round blue cell tumors. Interestingly, MHC class I gene expression (HLA-A/-B/-C) was correlated negatively with mRNAsi throughout all diagnostic entities: neuroblastomas (NB) (n = 88, r = -0.41, p < 0.001), the Ewing's sarcoma family of tumors (ESFT) (n = 117, r = -0.46, p < 0.001), rhabdomyosarcomas (RMS) (n = 158, r = -0.5, p < 0.001), Wilms tumors (WT) (n = 224, r = -0.39, p < 0.001), and central nervous system-primitive neuroectodermal tumors CNS-PNET (r = -0.49, p < 0.001), with the exception of medulloblastoma (MB) (n = 76, r = -0.24, p = 0.06). The negative correlation of MHC class I and mRNAsi was independent of clinical features in NB, RMS, and WT. In NB and WT, increased MHC class I was correlated negatively with tumor stage. RMS patients with a high expression of MHC class I and abundant CD8 T cells showed a prolonged overall survival (n = 148, p = 0.004). Possibly, low MHC class I expression and stemness in pediatric tumors are remnants of prenatal tumorigenesis from multipotent precursor cells. Further studies are needed to assess the usefulness of stemness and MHC class I as predictive markers.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mueller, Linda UNSPECIFIED UNSPECIFIED UNSPECIFIED Kschischo, Maik UNSPECIFIED UNSPECIFIED UNSPECIFIED Vokuhl, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Stahl, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Guetgemann, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-669683
DOI:	10.3390/cancers14153584
Journal or Publication Title:	Cancers
Volume:	14
Number:	15
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NCBI GEO; LANDSCAPE; ANTIGENS; NEUROBLASTOMA Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66968