PMID- 31161312 OWN - NLM STAT- MEDLINE DCOM- 20200619 LR - 20211210 IS - 1432-1440 (Electronic) IS - 0946-2716 (Linking) VI - 97 IP - 8 DP - 2019 Aug TI - Tumor cells endowed with professional antigen-presenting cell functions prime PBLs to generate antitumor CTLs. PG - 1139-1153 LID - 10.1007/s00109-019-01797-7 [doi] AB - Intrinsic genetic instability of tumor cells leads to continuous production of mutated proteins referred to as tumor-specific neoantigens. Generally, they are recognized as nonself products by the host immune system. However, an effective adaptive response clearing neoantigen-expressing cells is lost in tumor diseases. Most advanced therapeutic strategies aim at inducing neoantigen-specific immune activation through personalized approaches. They include tumor cell exome sequencing, human leukocyte antigen (HLA) typing, synthesis, and injection of peptides/RNA with adjuvants. Here, we propose an innovative method to induce a CD8(+) T cytotoxic lymphocyte (CTL) immune response against tumor neoantigens bypassing the steps needed in current therapeutic strategies of personalized vaccination. We assumed that tumor cells can be the most efficient and precise factory of major histocompatibility complex (MHC) class I-associated, tumor neoantigen-derived peptides. Hence, endowing tumor cells with professional antigen-presenting functions would prime CD8(+) T lymphocytes towards a response against nonself tumor antigens. To explore this possibility, both adenocarcinoma and melanoma human cells were engineered to express both CD80 and CD86 costimulatory molecules. HLA-matched lymphocytes were then primed through cocultivation with the engineered tumor cells. The generation of tumor-specific CD8(+) T lymphocytes was tested through the combined analysis of cell activation markers, formation of immunologic synapses, generation of tumor antigen-specific CD8(+) T lymphocytes, and cytotoxic activity. Our data consistently indicate that tumor cells endowed with professional antigen-presenting functions can generate an effective tumor-specific CTL immune response. This finding may open avenues towards the development of innovative antitumor immunotherapies. KEY MESSAGES: We established a novel method to induce antitumor CTLs without a need to identify TAAs and/or tumor neoantigens. This strategy relies on transducing tumor cells with a retroviral vector expressing both CD80 and CD86. In this way, tumor cells prime naive CD8(+) T lymphocytes in a way that CTLs killing the same tumor cells are generated. These findings open the way towards preclinical assays in the perspective to introduce this antitumor immunotherapy strategy in clinic. FAU - Chiozzini, Chiara AU - Chiozzini C AD - National Center for Global Health, Istituto Superiore di Sanita (ISS), Viale Regina Elena 299, 00161, Rome, Italy. FAU - Olivetta, Eleonora AU - Olivetta E AD - National Center for Global Health, Istituto Superiore di Sanita (ISS), Viale Regina Elena 299, 00161, Rome, Italy. FAU - Sanchez, Massimo AU - Sanchez M AD - Core Facilities, ISS, Viale Regina Elena 299, 00161, Rome, Italy. FAU - Arenaccio, Claudia AU - Arenaccio C AD - National Center for Global Health, Istituto Superiore di Sanita (ISS), Viale Regina Elena 299, 00161, Rome, Italy. FAU - Ferrantelli, Flavia AU - Ferrantelli F AD - National Center for Global Health, Istituto Superiore di Sanita (ISS), Viale Regina Elena 299, 00161, Rome, Italy. FAU - Leone, Patrizia AU - Leone P AD - National Center for Global Health, Istituto Superiore di Sanita (ISS), Viale Regina Elena 299, 00161, Rome, Italy. FAU - Federico, Maurizio AU - Federico M AD - National Center for Global Health, Istituto Superiore di Sanita (ISS), Viale Regina Elena 299, 00161, Rome, Italy. maurizio.federico@iss.it. LA - eng PT - Journal Article DEP - 20190603 PL - Germany TA - J Mol Med (Berl) JT - Journal of molecular medicine (Berlin, Germany) JID - 9504370 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) SB - IM MH - *Antigen Presentation MH - *Antigens, Neoplasm/genetics/immunology MH - *Cancer Vaccines/genetics/immunology MH - Coculture Techniques MH - *Cytotoxicity, Immunologic MH - *Dendritic Cells/immunology/pathology MH - HEK293 Cells MH - Humans MH - MCF-7 Cells MH - *Neoplasms/genetics/immunology/pathology MH - *T-Lymphocytes, Cytotoxic/immunology/pathology OTO - NOTNLM OT - Anticancer immunotherapy OT - Antigen-presenting cells OT - CTLs OT - MCF-7 cells OT - Melanoma cells OT - Retroviral vectors OT - Tumor neoantigens EDAT- 2019/06/05 06:00 MHDA- 2020/06/20 06:00 CRDT- 2019/06/05 06:00 PHST- 2018/09/19 00:00 [received] PHST- 2019/05/13 00:00 [accepted] PHST- 2019/05/08 00:00 [revised] PHST- 2019/06/05 06:00 [pubmed] PHST- 2020/06/20 06:00 [medline] PHST- 2019/06/05 06:00 [entrez] AID - 10.1007/s00109-019-01797-7 [pii] AID - 10.1007/s00109-019-01797-7 [doi] PST - ppublish SO - J Mol Med (Berl). 2019 Aug;97(8):1139-1153. doi: 10.1007/s00109-019-01797-7. Epub 2019 Jun 3.