Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide due to high recurrence rates after curative treatment and being frequently diagnosed at an advanced stage. Immune-checkpoint inhibition (ICPI) has yielded impressive clinical successes in a variety of solid...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2131096 |
| _version_ | 1811196179925434368 |
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| author | Lisanne Noordam Monique T.A. de Beijer Shanta Mancham Isabel Vogler Patrick P.C. Boor Valeska de Ruiter Robbie Luijten Jan N.M. IJzermans Ugur Sahin Marco J. Bruno Dave Sprengers Sonja I. Buschow Jaap Kwekkeboom |
| author_facet | Lisanne Noordam Monique T.A. de Beijer Shanta Mancham Isabel Vogler Patrick P.C. Boor Valeska de Ruiter Robbie Luijten Jan N.M. IJzermans Ugur Sahin Marco J. Bruno Dave Sprengers Sonja I. Buschow Jaap Kwekkeboom |
| author_sort | Lisanne Noordam |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide due to high recurrence rates after curative treatment and being frequently diagnosed at an advanced stage. Immune-checkpoint inhibition (ICPI) has yielded impressive clinical successes in a variety of solid cancers, however results in treatment of HCC have been modest. Vaccination could be a promising treatment to synergize with ICPI and enhance response rates. Cancer testis antigens (CTAs) were recently discovered to be widely expressed in HCC and expression in macroscopically tumor-free tissues correlated with recurrence, implying the presence of micro-satellites. To determine whether CTAs are immunogenic in HCC patients, we analyzed systemic T-cell and humoral responses against seven CTAs in 38 HCC patients using a multitude of techniques; flowcytometry, ELISA and whole antigen and peptide stimulation assays. CTA-specific T-cells were detected in all (25/25) analyzed patients, of which most had a memory phenotype but did not exhibit unequivocal signs of chronic stimulation or recent antigen encounter. Proliferative CD4+ and CD8+ T-cell responses against these CTAs were found in 14/16 analyzed HCC patients. CTA-peptide stimulation-induced granzyme B, IL2, and TNFa in 8/8 analyzed patients, including two MAGEA1 peptides included based on in silico prediction. Finally, IgG responses were observed in 13/32 patients, albeit with low titers. The presence of CD4+ and CD8+ T-cells and IgG responses shows the immunogenicity of these CTAs in HCC-patients. We hypothesize that vaccines based on these tumor-specific antigens may boost preexisting CTA-specific immunity and could enhance therapeutic efficacy of ICPI in advanced HCC. |
| first_indexed | 2024-04-12T00:55:24Z |
| format | Article |
| id | doaj.art-157b3da14c4742598e466ea3411e9ddf |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-12T00:55:24Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-157b3da14c4742598e466ea3411e9ddf2022-12-22T03:54:38ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2131096Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patientsLisanne Noordam0Monique T.A. de Beijer1Shanta Mancham2Isabel Vogler3Patrick P.C. Boor4Valeska de Ruiter5Robbie Luijten6Jan N.M. IJzermans7Ugur Sahin8Marco J. Bruno9Dave Sprengers10Sonja I. Buschow11Jaap Kwekkeboom12Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsBioNTech SE, Mainz, GermanyDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsBioNTech SE, Mainz, GermanyDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsDepartment of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The NetherlandsHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide due to high recurrence rates after curative treatment and being frequently diagnosed at an advanced stage. Immune-checkpoint inhibition (ICPI) has yielded impressive clinical successes in a variety of solid cancers, however results in treatment of HCC have been modest. Vaccination could be a promising treatment to synergize with ICPI and enhance response rates. Cancer testis antigens (CTAs) were recently discovered to be widely expressed in HCC and expression in macroscopically tumor-free tissues correlated with recurrence, implying the presence of micro-satellites. To determine whether CTAs are immunogenic in HCC patients, we analyzed systemic T-cell and humoral responses against seven CTAs in 38 HCC patients using a multitude of techniques; flowcytometry, ELISA and whole antigen and peptide stimulation assays. CTA-specific T-cells were detected in all (25/25) analyzed patients, of which most had a memory phenotype but did not exhibit unequivocal signs of chronic stimulation or recent antigen encounter. Proliferative CD4+ and CD8+ T-cell responses against these CTAs were found in 14/16 analyzed HCC patients. CTA-peptide stimulation-induced granzyme B, IL2, and TNFa in 8/8 analyzed patients, including two MAGEA1 peptides included based on in silico prediction. Finally, IgG responses were observed in 13/32 patients, albeit with low titers. The presence of CD4+ and CD8+ T-cells and IgG responses shows the immunogenicity of these CTAs in HCC-patients. We hypothesize that vaccines based on these tumor-specific antigens may boost preexisting CTA-specific immunity and could enhance therapeutic efficacy of ICPI in advanced HCC.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2131096Liver neoplasmstumor-associated antigensimmunotherapyvaccination |
| spellingShingle | Lisanne Noordam Monique T.A. de Beijer Shanta Mancham Isabel Vogler Patrick P.C. Boor Valeska de Ruiter Robbie Luijten Jan N.M. IJzermans Ugur Sahin Marco J. Bruno Dave Sprengers Sonja I. Buschow Jaap Kwekkeboom Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients OncoImmunology Liver neoplasms tumor-associated antigens immunotherapy vaccination |
| title | Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients |
| title_full | Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients |
| title_fullStr | Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients |
| title_full_unstemmed | Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients |
| title_short | Systemic T-cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients |
| title_sort | systemic t cell and humoral responses against cancer testis antigens in hepatocellular carcinoma patients |
| topic | Liver neoplasms tumor-associated antigens immunotherapy vaccination |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2131096 |
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