Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells
Attempts to develop a therapeutic vaccine against human papillomavirus (HPV)-induced malignancies have mostly not been clinically successful to date. One reason may be the hypoxic microenvironment present in most tumors, including cervical cancer. Hypoxia dysregulates the levels of human leukocyte a...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
21 October 2022
|
| In: |
Frontiers in immunology
Year: 2022, Volume: 13, Pages: 1-15 |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2022.918528 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fimmu.2022.918528 Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.918528 
|
| Author Notes: | Nitya Mohan, Kathrin Wellach, Ceren Özerdem, Nisha Veits, Jonas D. Förster, Sophia Foehr, Maria Bonsack and Angelika B. Riemer |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1837061076 | ||
| 003 | DE-627 | ||
| 005 | 20260210120151.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230220s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2022.918528 |2 doi | |
| 035 | |a (DE-627)1837061076 | ||
| 035 | |a (DE-599)KXP1837061076 | ||
| 035 | |a (OCoLC)1389534341 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Mohan, Nitya |d 1989- |e VerfasserIn |0 (DE-588)1247084582 |0 (DE-627)1780540566 |4 aut | |
| 245 | 1 | 0 | |a Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells |c Nitya Mohan, Kathrin Wellach, Ceren Özerdem, Nisha Veits, Jonas D. Förster, Sophia Foehr, Maria Bonsack and Angelika B. Riemer |
| 264 | 1 | |c 21 October 2022 | |
| 300 | |a 15 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 20.02.2023 | ||
| 520 | |a Attempts to develop a therapeutic vaccine against human papillomavirus (HPV)-induced malignancies have mostly not been clinically successful to date. One reason may be the hypoxic microenvironment present in most tumors, including cervical cancer. Hypoxia dysregulates the levels of human leukocyte antigen (HLA) class I molecules in different tumor entities, impacts the function of cytotoxic T cells, and leads to decreased protein levels of the oncoproteins E6 and E7 in HPV-transformed cells. Therefore, we investigated the effect of hypoxia on the presentation of HPV16 E6- and E7-derived epitopes in cervical cancer cells and its effect on epitope-specific T cell cytotoxicity. Hypoxia induced downregulation of E7 protein levels in all analyzed cell lines, as assessed by Western blotting. However, contrary to previous reports, no perturbation of antigen processing and presentation machinery (APM) components and HLA-A2 surface expression upon hypoxia treatment was detected by mass spectrometry and flow cytometry, respectively. Cytotoxicity assays performed in hypoxic conditions showed differential effects on the specific killing of HPV16-positive cervical cancer cells by epitope-specific CD8+ T cell lines in a donor- and peptide-specific manner. Effects of hypoxia on the expression of PD-L1 were ruled out by flow cytometry analysis. Altogether, our results under hypoxia show a decreased expression of E6 and E7, but an intact APM, and epitope- and donor-dependent effects on T cell cytotoxicity towards HPV16-positive target cells. This suggests that successful immunotherapies can be developed for hypoxic HPV-induced cervical cancer, with careful choice of target epitopes, and ideally in combination with hypoxia-alleviating measures. | ||
| 700 | 1 | |a Wellach, Kathrin |d 1995- |e VerfasserIn |0 (DE-588)1188440403 |0 (DE-627)1667391542 |4 aut | |
| 700 | 1 | |a Özerdem, Ceren |e VerfasserIn |4 aut | |
| 700 | 1 | |a Veits, Nisha |e VerfasserIn |4 aut | |
| 700 | 1 | |a Förster, Jonas D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Foehr, Sophia |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bonsack, Maria |e VerfasserIn |4 aut | |
| 700 | 1 | |a Riemer, Angelika |e VerfasserIn |0 (DE-588)1167191420 |0 (DE-627)1030878013 |0 (DE-576)511025688 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d Lausanne : Frontiers Media, 2010 |g 13(2022), Artikel-ID 918528, Seite 1-15 |h Online-Ressource |w (DE-627)657998354 |w (DE-600)2606827-8 |w (DE-576)343624834 |x 1664-3224 |7 nnas |a Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g elocationid:918528 |g pages:1-15 |g extent:15 |a Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells |
| 856 | 4 | 0 | |u https://doi.org/10.3389/fimmu.2022.918528 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |7 1 |
| 856 | 4 | 0 | |u https://www.frontiersin.org/articles/10.3389/fimmu.2022.918528 |x Verlag |z lizenzpflichtig |3 Volltext |7 1 |
| 951 | |a AR | ||
| 992 | |a 20230220 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 1167191420 |a Riemer, Angelika |m 1167191420:Riemer, Angelika |d 50000 |e 50000PR1167191420 |k 0/50000/ |p 8 |y j | ||
| 998 | |g 1188440403 |a Wellach, Kathrin |m 1188440403:Wellach, Kathrin |d 140000 |e 140000PW1188440403 |k 0/140000/ |p 2 | ||
| 999 | |a KXP-PPN1837061076 |e 4274770117 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"physDesc":[{"extent":"15 S."}],"recId":"1837061076","type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"note":["Gesehen am 20.02.2023"],"title":[{"title_sort":"Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells","title":"Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells"}],"origin":[{"dateIssuedKey":"2022","dateIssuedDisp":"21 October 2022"}],"person":[{"display":"Mohan, Nitya","given":"Nitya","role":"aut","family":"Mohan"},{"display":"Wellach, Kathrin","given":"Kathrin","role":"aut","family":"Wellach"},{"display":"Özerdem, Ceren","role":"aut","given":"Ceren","family":"Özerdem"},{"display":"Veits, Nisha","family":"Veits","given":"Nisha","role":"aut"},{"display":"Förster, Jonas D.","family":"Förster","role":"aut","given":"Jonas D."},{"display":"Foehr, Sophia","role":"aut","given":"Sophia","family":"Foehr"},{"display":"Bonsack, Maria","role":"aut","given":"Maria","family":"Bonsack"},{"role":"aut","given":"Angelika","family":"Riemer","display":"Riemer, Angelika"}],"relHost":[{"pubHistory":["1.2010 -"],"origin":[{"publisher":"Frontiers Media","publisherPlace":"Lausanne","dateIssuedKey":"2010","dateIssuedDisp":"2010-"}],"note":["Gesehen am 07.11.13"],"type":{"bibl":"periodical","media":"Online-Ressource"},"language":["eng"],"part":{"pages":"1-15","year":"2022","text":"13(2022), Artikel-ID 918528, Seite 1-15","volume":"13","extent":"15"},"title":[{"title_sort":"Frontiers in immunology","title":"Frontiers in immunology"}],"id":{"issn":["1664-3224"],"eki":["657998354"],"zdb":["2606827-8"]},"physDesc":[{"extent":"Online-Ressource"}],"recId":"657998354","disp":"Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cellsFrontiers in immunology"}],"id":{"eki":["1837061076"],"doi":["10.3389/fimmu.2022.918528"]},"name":{"displayForm":["Nitya Mohan, Kathrin Wellach, Ceren Özerdem, Nisha Veits, Jonas D. Förster, Sophia Foehr, Maria Bonsack and Angelika B. Riemer"]}} | ||
| SRT | |a MOHANNITYAEFFECTSOFH2120 | ||