Impact of tumor heterogeneity and microenvironment in identifying neoantigens in a patient with ovarian cancer Journal Article

   

Authors:	Dao, T.; Klatt, M. G.; Korontsvit, T.; Mun, S. S.; Guzman, S.; Mattar, M.; Zivanovic, O.; Kyi, C. K.; Socci, N. D.; O’Cearbhaill, R. E.; Scheinberg, D. A.
Article Title:	Impact of tumor heterogeneity and microenvironment in identifying neoantigens in a patient with ovarian cancer
Abstract:	Identification of neoepitopes as tumor-specific targets remains challenging, especially for cancers with low mutational burden, such as ovarian cancer. To identify mutated human leukocyte antigen (HLA) ligands as potential targets for immunotherapy in ovarian cancer, we combined mass spectrometry analysis of the major histocompatibility complex (MHC) class I peptidomes of ovarian cancer cells with parallel sequencing of whole exome and RNA in a patient with high-grade serous ovarian cancer. Four of six predicted mutated epitopes capable of binding to HLA-A*02:01 induced peptide-specific T cell responses in blood from healthy donors. In contrast, all six peptides failed to induce autologous peptide-specific response by T cells in peripheral blood or tumor-infiltrating lymphocytes from ascites of the patient. Surprisingly, T cell responses against a low-affinity p53-mutant Y220C epitope were consistently detected in the patient with either unprimed or in vitro peptide-stimulated T cells even though the patient’s primary tumor did not bear this mutation. Our results demonstrated that tumor heterogeneity and distinct immune microenvironments within a patient should be taken into consideration for identification of immunogenic neoantigens. T cell responses to a driver gene-derived p53 Y220C mutation in ovarian cancer warrant further study. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Keywords:	ovarian cancer; mass spectrometry; immunotherapy; t cell response; parallel sequencing; neoepitopes
Journal Title:	Cancer Immunology, Immunotherapy
Volume:	70
Issue:	5
ISSN:	0340-7004
Publisher:	Springer
Date Published:	2021-05-01
Start Page:	1189
End Page:	1202
Language:	English
DOI:	10.1007/s00262-020-02764-9
PUBMED:	33123756
PROVIDER:	scopus
PMCID:	PMC8053669
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85094207207&doi=10.1007%2fs00262-020-02764-9&partnerID=40&md5=1aeab113d2967660d51a85adc66e4b2c
Notes:	Article -- Export Date: 3 May 2021 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/180231