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Cancers
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Combination Immunotherapy for Cancer Treatment
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Combination Immunotherapy for Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 10 February 2025 | Viewed by 8931

Special Issue Editor

Dr. Carlos Alberto Barrero

E-Mail Website
Guest Editor
Proteomics and Metabolomics Facility, Moulder Center for Drug Discovery Research, Temple University, Philadelphia, PA 19140, USA
Interests: cancer immunotherapy; proteomics; metabolomics; diabetes; COPD; HIV

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to exploring the fascinating field of combination immunotherapy and its potential to revolutionize cancer treatment. In recent years, immunotherapy has emerged as an exciting approach in the fight against cancer, harnessing the power of the immune system to target and destroy cancer cells. However, single-agent immunotherapy has shown limitations in achieving complete and durable responses in all patients. That is where combination immunotherapy comes into play. By combining different immunotherapeutic agents, such as immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell transfer, researchers and clinicians aim to enhance the effectiveness of treatment and overcome resistance mechanisms. Original research work and review articles covering the aforementioned or any novel biologics-mediated cancer treatment or immunotherapy will be considered for this Special Issue.

Dr. Carlos Alberto Barrero
Guest Editor

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
  • immune checkpoint inhibitor
  • cancer vaccine
  • novel cancer therapy
  • treatment

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Published Papers (5 papers)

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Research

Jump to: Review

17 pages, 4146 KiB  
Article
Definition of a Multi-Omics Signature for Esophageal Adenocarcinoma Prognosis Prediction
by Luca Lambroia, Carola Maria Conca Dioguardi, Simone Puccio, Andrea Pansa, Giorgia Alvisi, Gianluca Basso, Javier Cibella, Federico Simone Colombo, Salvatore Marano, Silvia Basato, Rita Alfieri, Simone Giudici, Carlo Castoro and Clelia Peano
Cancers 2024, 16(15), 2748; https://doi.org/10.3390/cancers16152748 - 1 Aug 2024
Viewed by 1762
Abstract
Esophageal cancer is a highly lethal malignancy, representing 5% of all cancer-related deaths. The two main subtypes are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most research has focused on ESCC, few studies have analyzed EAC for transcriptional signatures linked [...] Read more.
Esophageal cancer is a highly lethal malignancy, representing 5% of all cancer-related deaths. The two main subtypes are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). While most research has focused on ESCC, few studies have analyzed EAC for transcriptional signatures linked to diagnosis or prognosis. In this study, we utilized single-cell RNA sequencing and bulk RNA sequencing to identify specific immune cell types that contribute to anti-tumor responses, as well as differentially expressed genes (DEGs). We have characterized transcriptional signatures, validated against a wide cohort of TCGA patients, that are capable of predicting clinical outcomes and the prognosis of EAC post-surgery with efficacy comparable to the currently accepted prognostic factors. In conclusion, our findings provide insights into the immune landscape and therapeutic targets of EAC, proposing novel immunological biomarkers for predicting prognosis, aiding in patient stratification for post-surgical outcomes, follow-up, and personalized adjuvant therapy decisions. Full article
(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)
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14 pages, 8994 KiB  
Article
Release of Exosomal PD-L1 in Bone and Soft Tissue Sarcomas and Its Relationship to Radiotherapy
by Keisuke Yoshida, Kunihiro Asanuma, Yumi Matsuyama, Takayuki Okamoto, Tomohito Hagi, Tomoki Nakamura and Akihiro Sudo
Cancers 2024, 16(13), 2489; https://doi.org/10.3390/cancers16132489 - 8 Jul 2024
Viewed by 1092
Abstract
(1) Background: Exosomal PD-L1 has garnered attention owing to its role in instigating systemic immune suppression. The objective of this study is to elucidate whether bone and soft tissue sarcoma cells possess the capacity to secrete functionally active exosomal PD-L1 and whether radiotherapy [...] Read more.
(1) Background: Exosomal PD-L1 has garnered attention owing to its role in instigating systemic immune suppression. The objective of this study is to elucidate whether bone and soft tissue sarcoma cells possess the capacity to secrete functionally active exosomal PD-L1 and whether radiotherapy (RT) induces the exosomal PD-L1 release. (2) Methods: Human osteosarcoma cell line 143B and human fibrosarcoma cell line HT1080 were utilized. Exosomes were isolated from the culture medium and blood via ultracentrifugation. The expression of PD-L1 on both tumor cells and exosomes was evaluated. The inhibitory effect on PBMC was employed to assess the activity of exosomal PD-L1. Post radiotherapy, changes in PD-L1 expression were compared. (3) Results: Exosomal PD-L1 was detected in the culture medium of tumor cells but was absent in the culture medium of PD-L1 knockout cells. Exosomal PD-L1 exhibited an inhibitory effect on PBMC activation. In tumor-bearing mice, human-derived exosomal PD-L1 was detected in the bloodstream. Following radiotherapy, tumor cells upregulated PD-L1, and human-derived exosomal PD-L1 were detected in the bloodstream. (4) Conclusions: Exosomal PD-L1 emanates from bone and soft tissue sarcoma cells and is disseminated into the circulatory system. The levels of PD-L1 in tumor cells and the release of exosomal PD-L1 were augmented after irradiation with RT. Full article
(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)
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18 pages, 1119 KiB  
Article
Intracranial Efficacy of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in Real-World Patients with Non-Small-Cell Lung Cancer and EGFR or ALK Alterations
by Marcus Rathbone, Conor O’Hagan, Helen Wong, Adeel Khan, Timothy Cook, Sarah Rose, Jonathan Heseltine and Carles Escriu
Cancers 2024, 16(7), 1249; https://doi.org/10.3390/cancers16071249 - 22 Mar 2024
Viewed by 2079
Abstract
Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients [...] Read more.
Contrary to Pemetrexed-containing chemo-immunotherapy studies, Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel (ABCP) treatment has consistently shown clinical benefit in prospective studies in patients with lung cancer and actionable mutations, where intracranial metastases are common. Here, we aimed to describe the real-life population of patients fit to receive ABCP after targeted therapy and quantify its clinical effect in patients with brain metastases. Patients treated in Cheshire and Merseyside between 2019 and 2022 were identified. Data were collected retrospectively. A total of 34 patients with actionable EGFR or ALK alterations had treatment with a median age of 59 years (range 32–77). The disease control rate was 100% in patients with PDL1 ≥ 1% (n = 10). In total, 19 patients (56%) had brain metastases before starting ABCP, 17 (50%) had untreated CNS disease, and 4 (22%) had PDL1 ≥ 1%. The median time to symptom improvement was 12.5 days (range 4–21 days), with 74% intracranial disease control rates and 89.5% synchronous intracranial (IC) and extracranial (EC) responses. IC median Progression Free Survival (mPFS) was 6.48 months, EC mPFS was 10.75 months, and median Overall Survival 11.47 months. ABCP in real-life patients with brain metastases (treated or untreated) was feasible and showed similar efficacy to that described in patients without actionable mutations treated with upfront chemo-immunotherapy. Full article
(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)
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Review

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18 pages, 1653 KiB  
Review
Overcoming Resistance to Checkpoint Inhibitors with Combination Strategies in the Treatment of Non-Small Cell Lung Cancer
by Amanda Reyes, Ramya Muddasani and Erminia Massarelli
Cancers 2024, 16(16), 2919; https://doi.org/10.3390/cancers16162919 - 22 Aug 2024
Cited by 3 | Viewed by 1488
Abstract
Lung cancer continues to contribute to the highest percentage of cancer-related deaths worldwide. Advancements in the treatment of non-small cell lung cancer like immune checkpoint inhibitors have dramatically improved survival and long-term disease response, even in curative and perioperative settings. Unfortunately, resistance develops [...] Read more.
Lung cancer continues to contribute to the highest percentage of cancer-related deaths worldwide. Advancements in the treatment of non-small cell lung cancer like immune checkpoint inhibitors have dramatically improved survival and long-term disease response, even in curative and perioperative settings. Unfortunately, resistance develops either as an initial response to treatment or more commonly as a progression after the initial response. Several modalities have been utilized to combat this. This review will focus on the various combination treatments with immune checkpoint inhibitors including the addition of chemotherapy, various immunotherapies, radiation, antibody–drug conjugates, bispecific antibodies, neoantigen vaccines, and tumor-infiltrating lymphocytes. We discuss the status of these agents when used in combination with immune checkpoint inhibitors with an emphasis on lung cancer. The early toxicity signals, tolerability, and feasibility of implementation are also reviewed. We conclude with a discussion of the next steps in treatment. Full article
(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)
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24 pages, 1778 KiB  
Review
Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma
by Chenkai Mao, Maria Poimenidou and Brian T. Craig
Cancers 2024, 16(16), 2865; https://doi.org/10.3390/cancers16162865 - 17 Aug 2024
Viewed by 1778
Abstract
Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few [...] Read more.
Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few new therapies to substantially improve outcomes to current levels. Given the persistent challenge of relapse and therapeutic resistance, there is an urgent need for new effective and tolerable treatment options for high-risk NBL. Recent breakthroughs in immune checkpoint inhibitor (ICI) therapeutics have not translated into high-risk NBL, like many other major pediatric solid tumors. Given the suppressed tumor microenvironment (TME), single ICIs like anti-CTLA4 and anti-PD1 have not demonstrated significant antitumor response rates. Meanwhile, emerging studies are reporting novel advancements in GD2-based therapies, targeted therapies, nanomedicines, and other immunotherapies such as adoptive transfer of natural killer (NK) cells and chimeric antigen receptors (CARs), and these hold interesting promise for the future of high-risk NBL patient care. Herein, we summarize the current state of the art in NBL therapeutic options and highlight the unique challenges posed by NBL that have limited the successful adoption of immune-modifying therapies. Through this review, we aim to direct the field’s attention to opportunities that may benefit from a combination immunotherapy strategy. Full article
(This article belongs to the Special Issue Combination Immunotherapy for Cancer Treatment)
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