Immunotherapy: A New Challenge in Treating Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 18964

Special Issue Editor

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
Interests: cancer therapy; HCC; immunotherapy; notch signaling; flow cytometry
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Special Issue Information

Dear Colleagues,

Immunotherapy, and specifically checkpoint inhibitors, have a remarkably impressive, positive impact on clinical outcomes in an ever-increasing number of clinical settings. Immunotherapy advances can be applied to several immune-mediated pathologies, and the success achieved with some types of immunotherapies in recent years is revealing new ways to explore and manipulate the immune system to our benefit.

This Special Issue welcomes original research papers or comprehensive reviews addressing every aspect of this topic, including function and regulation in biology and medicine. Our aim is for interdisciplinary applications of the knowledge to stimulate future research.

Dr. Catia Giovannini
Guest Editor

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Keywords

  • immunotherapy
  • checkpoint inhibitors
  • cancers
  • human diseases
  • combined treatments

Published Papers (5 papers)

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Research

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19 pages, 3468 KiB  
Article
Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions
Cells 2021, 10(8), 2044; https://doi.org/10.3390/cells10082044 - 10 Aug 2021
Cited by 15 | Viewed by 5099
Abstract
Drugs targeting immune checkpoint molecules have been found effective in melanoma, lung cancer, and other malignancies treatment. Recent studies on breast cancer demonstrated the significance of inhibitory anti-CTLA-4 and anti-PD-1 in the regulation of disease progression. However, seemingly the same types of breast [...] Read more.
Drugs targeting immune checkpoint molecules have been found effective in melanoma, lung cancer, and other malignancies treatment. Recent studies on breast cancer demonstrated the significance of inhibitory anti-CTLA-4 and anti-PD-1 in the regulation of disease progression. However, seemingly the same types of breast cancer do not always respond unambiguously to immunotherapy. Thus, here we set out to analyze the in vitro effects of inhibiting CTLA-4 and PD-1 on interactions between co-cultured lymphocytes and two selected breast adenocarcinoma cell lines. Breast cancer cells were co-cultured with lymphocytes to evaluate the effects of CTLA-4 and PD-1 inhibition. Proliferation, cell cycle, and viability assessment were measured in cancer cells. IFN-gamma, IL-10, perforin, granzyme B production, and CTLA-4 and PD-1 expression were analyzed in lymphocytes. We found that administration of anti-CTLA-4 improved the anti-cancer activity of T cells with reduced proliferation and viability of MDA-MB-231. Lack of response was observed in the context of MCF-7. In addition, differential expression of checkpoint proteins was found between studied cancer cells lines. Inhibition of molecules was followed by IL-10 and IFN-gamma decrease in lymphocytes co-cultured with MDA-MB-231, not demonstrated in reference to MCF-7. Furthermore, CTLA-4 blockage was associated with reduction of CTLA-4+ and PD-1+ lymphocytes in MDA-MB-231, with a significant increase in MCF-7, reduced by anti-PD-1. Altogether, our study revealed that anti-CTLA-4 and anti-PD-1 treatment can improve lymphocytes effects on breast cancer cells. Favorable effects seemed to be related to breast cancer cells features as differential responses were reported. Novel blocking antibodies strategies should be tested for more effective cancer inhibition. Full article
(This article belongs to the Special Issue Immunotherapy: A New Challenge in Treating Cancer)
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Review

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25 pages, 1241 KiB  
Review
Recent Advances in CAR-Based Solid Tumor Immunotherapy
Cells 2023, 12(12), 1606; https://doi.org/10.3390/cells12121606 - 11 Jun 2023
Cited by 6 | Viewed by 2931
Abstract
Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment [...] Read more.
Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design—such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells—have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors. Full article
(This article belongs to the Special Issue Immunotherapy: A New Challenge in Treating Cancer)
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15 pages, 333 KiB  
Review
Plasmacytoid Dendritic Cells and Cancer Immunotherapy
Cells 2022, 11(2), 222; https://doi.org/10.3390/cells11020222 - 11 Jan 2022
Cited by 24 | Viewed by 3991
Abstract
Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement [...] Read more.
Despite largely disappointing clinical trials of dendritic cell (DC)-based vaccines, recent studies have shown that DC-mediated cross-priming plays a critical role in generating anti-tumor CD8 T cell immunity and regulating anti-tumor efficacy of immunotherapies. These new findings thus support further development and refinement of DC-based vaccines as mono-immunotherapy or combinational immunotherapies. One exciting development is recent clinical studies with naturally circulating DCs including plasmacytoid DCs (pDCs). pDC vaccines were particularly intriguing, as pDCs are generally presumed to play a negative role in regulating T cell responses in tumors. Similarly, DC-derived exosomes (DCexos) have been heralded as cell-free therapeutic cancer vaccines that are potentially superior to DC vaccines in overcoming tumor-mediated immunosuppression, although DCexo clinical trials have not led to expected clinical outcomes. Using a pDC-targeted vaccine model, we have recently reported that pDCs required type 1 conventional DCs (cDC1s) for optimal cross-priming by transferring antigens through pDC-derived exosomes (pDCexos), which also cross-prime CD8 T cells in a bystander cDC-dependent manner. Thus, pDCexos could combine the advantages of both cDC1s and pDCs as cancer vaccines to achieve better anti-tumor efficacy. In this review, we will focus on the pDC-based cancer vaccines and discuss potential clinical application of pDCexos in cancer immunotherapy. Full article
(This article belongs to the Special Issue Immunotherapy: A New Challenge in Treating Cancer)
25 pages, 1057 KiB  
Review
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables
Cells 2021, 10(11), 3166; https://doi.org/10.3390/cells10113166 - 14 Nov 2021
Cited by 19 | Viewed by 3026
Abstract
Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of [...] Read more.
Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41–50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases. Full article
(This article belongs to the Special Issue Immunotherapy: A New Challenge in Treating Cancer)
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22 pages, 564 KiB  
Review
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic–Pathologic Correlations
Cells 2021, 10(11), 3165; https://doi.org/10.3390/cells10113165 - 14 Nov 2021
Cited by 8 | Viewed by 2863
Abstract
Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. [...] Read more.
Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic–pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized. Full article
(This article belongs to the Special Issue Immunotherapy: A New Challenge in Treating Cancer)
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