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Cancer Immunotherapy: Recent Advances and Prospects
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Cancer Immunotherapy: Recent Advances and Prospects

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 8208

Special Issue Editors

Prof. Dr. Il-Kang Na

E-Mail Website
Guest Editor
Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin
German Cancer Consortium (DKTK), partner site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany
Experimental and Clinical Research Center (ECRC), Berlin, Germany
Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany
Interests: cancer immuotherapy; biomarker; immune modulation and reconstitution
Dr. Antonia Busse

E-Mail Website
Guest Editor
Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
Interests: cancer immuotherapy; biomarker; immune modulation and reconstitution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the era of emerging cancer immunotherapy, new challenges have arisen due to treatment-induced resistance mechanisms on the tumor side and alterations of innate and adaptive patients’ immune systems. Each cancer-specific therapy as well as each immunotherapy results in dynamic tumor immune interaction. With a better understanding of these interactions, not only novel combination therapies but also smart sequencing strategies can be developed.

This Special Issue aims to publish research articles, reviews, and perspectives that concentrate on clinical/translational cancer immunotherapy, including in vitro and in vivo studies about novel immunotherapeutic approaches, therapy-induced immunomodulation and immunotherapy biomarkers.

Prof. Dr. Il-Kang Na
PD Dr. Antonia Busse
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Immunotherapy
  • Checkpoint inhibitor therapy
  • Adoptive T cell therapy
  • Resistance mechanisms
  • Immune modulation
  • Immune reconstitution
  • Combination therapy
  • Immunosuppression
  • Biomarker
  • In vitro studies
  • In vivo studies

Published Papers (3 papers)

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Research

22 pages, 2467 KiB  
Article
Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens
by Paul Schossig, Ebru Coskun, Ruza Arsenic, David Horst, Jalid Sehouli, Eva Bergmann, Nadine Andresen, Christian Sigler, Antonia Busse, Ulrich Keller and Sebastian Ochsenreither
Int. J. Mol. Sci. 2023, 24(3), 2292; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032292 - 24 Jan 2023
Viewed by 1786
Abstract
Adoptive T cell-receptor therapy (ACT) could represent a promising approach in the targeted treatment of epithelial ovarian cancer (EOC). However, the identification of suitable tumor-associated antigens (TAAs) as targets is challenging. We identified and prioritized TAAs for ACT and other immunotherapeutic interventions in [...] Read more.
Adoptive T cell-receptor therapy (ACT) could represent a promising approach in the targeted treatment of epithelial ovarian cancer (EOC). However, the identification of suitable tumor-associated antigens (TAAs) as targets is challenging. We identified and prioritized TAAs for ACT and other immunotherapeutic interventions in EOC. A comprehensive list of pre-described TAAs was created and candidates were prioritized, using predefined weighted criteria. Highly ranked TAAs were immunohistochemically stained in a tissue microarray of 58 EOC samples to identify associations of TAA expression with grade, stage, response to platinum, and prognosis. Preselection based on expression data resulted in 38 TAAs, which were prioritized. Along with already published Cyclin A1, the TAAs KIF20A, CT45, and LY6K emerged as most promising targets, with high expression in EOC samples and several identified peptides in ligandome analysis. Expression of these TAAs showed prognostic relevance independent of molecular subtypes. By using a systematic vetting algorithm, we identified KIF20A, CT45, and LY6K to be promising candidates for immunotherapy in EOC. Results are supported by IHC and HLA-ligandome data. The described method might be helpful for the prioritization of TAAs in other tumor entities. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Recent Advances and Prospects)
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17 pages, 5297 KiB  
Article
Heterogeneity of Mismatch Repair Status and Microsatellite Instability between Primary Tumour and Metastasis and Its Implications for Immunotherapy in Colorectal Cancers
by Camille Evrard, Stéphane Messina, David Sefrioui, Éric Frouin, Marie-Luce Auriault, Romain Chautard, Aziz Zaanan, Marion Jaffrelot, Christelle De La Fouchardière, Thomas Aparicio, Romain Coriat, Julie Godet, Christine Silvain, Violaine Randrian, Jean-Christophe Sabourin, Rosine Guimbaud, Elodie Miquelestorena-Standley, Thierry Lecomte, Valérie Moulin, Lucie Karayan-Tapon, Gaëlle Tachon and David Tougeronadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(8), 4427; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084427 - 17 Apr 2022
Cited by 6 | Viewed by 2492
Abstract
Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status [...] Read more.
Deficient mismatch repair system (dMMR)/microsatellite instability (MSI) is found in about 5% of metastatic colorectal cancers (mCRCs) with a major therapeutic impact for immune checkpoint inhibitor (ICI) use. We conducted a multicentre study including all consecutive patients with a dMMR/MSI mCRC. MSI status was determined using the Pentaplex panel and expression of the four MMR proteins was evaluated by immunohistochemistry (IHC). The primary endpoint was the rate of discordance of dMMR/MSI status between primary tumours and paired metastases. We included 99 patients with a dMMR/MSI primary CRC and 117 paired metastases. Only four discrepancies (3.4%) with a dMMR/MSI primary CRC and a pMMR/MSS metastasis were initially identified and reviewed by expert pathologists and molecular biologists. Two cases were false discrepancies due to human or technical errors. One discordant case could not be confirmed due to the low level of tumour cells. The last case had a confirmed discrepancy with a dMMR/MSI primary CRC and a pMMR/MSS peritoneal metastasis. Our study demonstrated a high concordance rate of dMMR/MSI status between primary CRCs and their metastases. The analysis of one sample, either from the primary tumour or metastasis, with consistent dMMR and MSI status seems to be sufficient prior to treatment with ICI. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Recent Advances and Prospects)
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14 pages, 11966 KiB  
Communication
Simultaneous Genetic Ablation of PD-1, LAG-3, and TIM-3 in CD8 T Cells Delays Tumor Growth and Improves Survival Outcome
by Elisa Ciraolo, Stefanie Althoff, Josefine Ruß, Stanislav Rosnev, Monique Butze, Miriam Pühl, Marco Frentsch, Lars Bullinger and Il-Kang Na
Int. J. Mol. Sci. 2022, 23(6), 3207; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063207 - 16 Mar 2022
Cited by 7 | Viewed by 2975
Abstract
Immune checkpoint inhibitors (ICI) represented a step forward in improving the outcome of patients with various refractory solid tumors and several therapeutic regimens incorporating ICI have already been approved for a variety of tumor entities. However, besides remarkable long-term responses, checkpoint inhibition can [...] Read more.
Immune checkpoint inhibitors (ICI) represented a step forward in improving the outcome of patients with various refractory solid tumors and several therapeutic regimens incorporating ICI have already been approved for a variety of tumor entities. However, besides remarkable long-term responses, checkpoint inhibition can trigger severe immune-related adverse events in some patients. In order to improve safety of ICI as well as T cell therapy, we tested the feasibility of combining T cell-based immunotherapy with genetic disruption of checkpoint molecule expression. Therefore, we generated H-Y and ovalbumin antigen-specific CD8+ T cells with abolished PD-1, LAG-3, and TIM-3 expression through CRISPR/Cas9 technology. CD8+ T cells, subjected to PD-1, LAG-3, and TIM-3 genetic editing, showed a strong reduction in immune checkpoint molecule expression after in vitro activation, while no relevant reduction in responsiveness to in vitro stimulation was observed. At the same time, in B16-OVA tumor model, transferred genetically edited OT-1 CD8+ T cells promoted longer survival compared to control T cells and showed enhanced expansion without associated toxicity. Our study supports the notion that antigen-specific adoptive T cell therapy with concomitant genetic disruption of multiple checkpoint inhibitory receptors could represent an effective antitumor immunotherapy approach with improved tolerability profile. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Recent Advances and Prospects)
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