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Cancers
Special Issues
Cancer Immunotherapy: Therapeutics and Mechanisms
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Cancer Immunotherapy: Therapeutics and Mechanisms

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

Deadline for manuscript submissions: closed (30 July 2024) | Viewed by 8843

Special Issue Editors

Dr. Jenny Bulgarelli

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Guest Editor
IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) "Dino Amadori" S.r.l., Via Piero Maroncelli, 40, 47014 Meldola, FC, Italy
Interests: immunotherapy; melanoma; immunology; immunomonitoring; T cell response; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals
Dr. Sara Pignatta

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Guest Editor
IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) "Dino Amadori" S.r.l., Via Piero Maroncelli, 40, 47014 Meldola, FC, Italy
Interests: immunotherapy; ATMP advanced therapy medicinal products; dendritic cell vaccine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Cancer immunotherapy has now revolutionized the field of oncology by prolonging the survival of patients. Novel treatment combinations and newly identified druggable targets will only expand the role of immunotherapy in the treatment of cancer in the decades to come. 

In this Special Issue, our focus is on anti-cancer immunotherapies and mechanisms of action of new immunotherapy combinations, especially those including cell therapy products.

There is an urgent need to find molecular and cellular predictive and prognostic biomarkers which can be integrated with clinical pathological and imaging data to improve the prediction of both cancer progression and the response to immunotherapy for the right patient at the right time.

This Special Issue will include (but is not limited to) original research and review articles on the following topics:

  • Anti-cancer vaccine development and efficacy evaluation;
  • Immunotherapies, adjuvants and immunomodulators;
  • Cell therapy developments and mechanisms of action;
  • Immunology mechanisms;
  • Immune response to immunotherapies.

We look forward to receiving your contributions.

You may choose our Joint Special Issue in Vaccines.

Dr. Jenny Bulgarelli
Dr. Sara Pignatta
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 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

  • cancer immunotherapies
  • cell therapies
  • immuno-oncology
  • immune response
  • immunological biomarkers
  • immunomodulation
  • tumor microenvironment
  • translational biology

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Published Papers (4 papers)

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Research

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19 pages, 12313 KiB  
Article
The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment
by Zhan Zhuang, Jinglin Zhou, Minglian Qiu, Jiamian Li, Zhuangheng Lin, Huihan Yi, Xuerong Liu, Changyu Huang, Binghua Tang, Bo Liu and Xu Li
Cancers 2024, 16(4), 832; https://doi.org/10.3390/cancers16040832 - 19 Feb 2024
Viewed by 1827
Abstract
In solid tumors, the formidable anti-tumor impact resulting from blocking the “don’t eat me” signal, arising from CD47–SIRPα interaction, is constrained, especially compared to its efficacy in hematopoietic malignancies. Activating macrophage anti-tumor activity not only necessitates the inhibition of the “don’t eat me” [...] Read more.
In solid tumors, the formidable anti-tumor impact resulting from blocking the “don’t eat me” signal, arising from CD47–SIRPα interaction, is constrained, especially compared to its efficacy in hematopoietic malignancies. Activating macrophage anti-tumor activity not only necessitates the inhibition of the “don’t eat me” signal, but also the activation of the “eat me” (pre-phagocyte) signal. Intriguingly, the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody (Ab) has been identified to stimulate Fc receptor-mediated active phagocytes in the tumor microenvironment, thereby generating “eat me” signals. This study postulates that concurrently targeting CD47 and CTLA4 could intensify the anti-tumor effects by simultaneously blocking the “don’t eat me” signal while triggering the “eat me” signal. The experimental data from this investigation confirm that the combined targeting of CD47 and CTLA4 enhances immunity against solid tumors in LLC cell-transplanted tumor-bearing mice. This effect is achieved by reducing myeloid-derived suppressor cell infiltration while increasing the presence of effector memory CD8+ T cells, NK1.1+ CD8+ T cells, and activated natural killer T cells. Meanwhile, combination therapy also alleviated anemia. Mechanistically, the anti-CD47 Ab is shown to upregulate CTLA4 levels in NSCLC cells by regulating Foxp1. Furthermore, targeting CD47 is demonstrated to promote tumor vascular normalization through the heightened infiltration of CD4+ T cells. These findings suggest that the dual targeting of CD47 and CTLA4 exerts anti-tumor effects by orchestrating the “eat me” and “don’t eat me” signals, reshaping the immune microenvironment, and fostering tumor vascular normalization. This combined therapeutic approach emerges as a potent strategy for effectively treating solid tumors. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Therapeutics and Mechanisms)
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19 pages, 4625 KiB  
Article
Effects of Combinatory In Vitro Treatment with Immune Checkpoint Inhibitors and Cytarabine on the Anti-Cancer Immune Microenvironment in De Novo AML Patients
by Łukasz Bołkun, Aleksandra Starosz, Anna Krętowska-Grunwald, Tomasz Wasiluk, Alicja Walewska, Agnieszka Wierzbowska, Marcin Moniuszko and Kamil Grubczak
Cancers 2024, 16(2), 462; https://doi.org/10.3390/cancers16020462 - 22 Jan 2024
Cited by 1 | Viewed by 1842
Abstract
Despite substantial progress in the diagnostic and therapeutic procedures, acute myeloid leukaemia (AML) still constitutes a significant problem for patients suffering from its relapses. A comprehensive knowledge of the disease’s molecular background has led to the development of targeted therapies, including immune checkpoint [...] Read more.
Despite substantial progress in the diagnostic and therapeutic procedures, acute myeloid leukaemia (AML) still constitutes a significant problem for patients suffering from its relapses. A comprehensive knowledge of the disease’s molecular background has led to the development of targeted therapies, including immune checkpoint inhibitors, and demonstrated beneficial effects on several types of cancer. Here, we aimed to assess in vitro the potential of the immune checkpoint blockage for supporting anti-cancer responses to the AML backbone therapy with cytarabine. PBMCs of AML patients were collected at admission and, following the therapy, eight complete remission (CR) and eight non-responders (NR) subjects were selected. We assessed the effects of the in vitro treatment of the cells with cytarabine and the immune checkpoint inhibitors: anti-CTLA-4, anti-PD-1, anti-PD-L1. The study protocol allowed us to evaluate the viability of the cancer and the immune cells, proliferation status, phenotype, and cytokine release. Anti-PD-L1 antibodies were found to exert the most beneficial effect on the activation of T cells, with a concomitant regulation of the immune balance through Treg induction. There was no direct influence on the blast cells; however, the modulation of the PD-1/PD-L1 axis supported the expansion of lymphocytes. Changes in the response between CR and NR patients might result from the differential expression of PD-1 and PD-L1, with lower levels in the latter group. The tested blockers appear to support the anti-cancer immune responses rather than directly improve the effects of cytarabine. In conclusion, checkpoint proteins’ modulators might improve the anti-cancer responses in the tumour environment. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Therapeutics and Mechanisms)
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12 pages, 1157 KiB  
Article
PD-1 Inhibitors in Elderly and Immunocompromised Patients with Advanced or Metastatic Cutaneous Squamous Cell Carcinoma
by Alexander Yakobson, Ashraf Abu Jama, Omar Abu Saleh, Regina Michlin and Walid Shalata
Cancers 2023, 15(16), 4041; https://doi.org/10.3390/cancers15164041 - 10 Aug 2023
Cited by 8 | Viewed by 2599
Abstract
Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of [...] Read more.
Cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common form of skin cancer, with aging and prolonged exposure to ultraviolet rays being the main causes of the disease. Cemiplimab and pembrolizumab recently gained regulatory approval for the treatment of locally advanced and metastatic cSCC—conditions that are not treatable by surgical resection and/or radiotherapy. Although the results from the clinical trials have been promising, these studies have not included immunosuppressed, elderly patients. In this study, we included all immunocompromised and immunocompetent patients over the age of 75 years diagnosed with locally advanced or metastatic cSCC and treated with cemiplimab or pembrolizumab. The median duration of follow-up from cSCC diagnosis was 35.6 months, 82.9% of patients were male, and the median age was 83 years old. The median progression-free survival was 8.94 months. The incidence of treatment-related adverse events was 85.6%, the majority of which were grades 1 or 2. The disease control rate was 91.4%, the complete response rate was 17.1%, the partial response rate was 51.4%, the stable disease rate was 23%, and the progressive disease rate was 8.7%. Based on this study, cemiplimab and pembrolizumab for the treatment of locally advanced or metastatic cSCC in elderly, immunocompromised patients are efficacious, with acceptable safety profiles. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Therapeutics and Mechanisms)
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Review

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21 pages, 1115 KiB  
Review
Mechanistic Insights into the Successful Development of Combination Therapy of Enfortumab Vedotin and Pembrolizumab for the Treatment of Locally Advanced or Metastatic Urothelial Cancer
by Caroline Taylor, Kamai M. Patterson, Devira Friedman, Silvia M. Bacot, Gerald M. Feldman and Tao Wang
Cancers 2024, 16(17), 3071; https://doi.org/10.3390/cancers16173071 - 4 Sep 2024
Viewed by 1947
Abstract
Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic [...] Read more.
Antibody–drug conjugates (ADCs) consist of an antibody backbone that recognizes and binds to a target antigen expressed on tumor cells and a small molecule chemotherapy payload that is conjugated to the antibody via a linker. ADCs are one of the most promising therapeutic modalities for the treatment of various cancers. However, many patients have developed resistance to this form of therapy. Extensive efforts have been dedicated to identifying an effective combination of ADCs with other types of anticancer therapies to potentially overcome this resistance. A recent clinical study demonstrated that a combination of the ADC enfortumab vedotin (EV) with the immune checkpoint inhibitor (ICI) pembrolizumab can achieve remarkable clinical efficacy as the first-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma (la/mUC)—leading to the first approval of a combination therapy of an ADC with an ICI for the treatment of cancer patients. In this review, we highlight knowledge and understanding gained from the successful development of EV and the combination therapy of EV with ICI for the treatment of la/mUC. Using urothelial carcinoma as an example, we will focus on dissecting the underlying mechanisms necessary for the development of this type of combination therapy for a variety of cancers. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Therapeutics and Mechanisms)
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