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Recent Advances in Immunotherapy for Solid Tumors

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 11589

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Special Issue Editors

Dr. Satoko Matsueda

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Guest Editor

Fresh Wind Biotechnologies, Houston, TX, USA
Interests: immunotherapy; translational research; immuno-oncology;preclinical study;clinical study;immune-monitoring; immune pProfiling; cancer vaccines;adoptive cell therapies

Dr. Yoshimi Arima

E-Mail Website
Guest Editor

Cancer Center, Fujita Health University, Toyoake, Japan
Interests: tumor biology; molecular biology; molecular pathology

Special Issue Information

Dear Colleagues,

The special issue titled "Recent Advances in Immunotherapy for Solid Cancer" presents a comprehensive overview of research highlighting the latest breakthroughs in the immunotherapy for solid tumors. The issue brings together state of art technologies and studies that delve into various aspects of immunotherapy, including novel treatment approaches, combination strategies, biomarkers, and immune-related adverse events. This special issue focus on the remarkable progress made in harnessing the immune system to battle solid cancers. It covers a wide range of topics, including, but are not limited to adoptive cell therapies, immune checkpoint inhibitors, monoclonal antibodies, small molecules, cytokines, cancer vaccines, and oncolytic viruses. Moreover, the issue explores the role of the tumor microenvironment, neoantigens, and immune escape mechanisms in shaping the efficacy of immunotherapeutic interventions.

In addition, the special issue emphasizes the importance of personalized medicine in immunotherapy, with articles focusing on patient-specific approaches such as neoantigen identification, immune profiling, biomarkers, and targeted therapies. The integration of genomics, transcriptomics, proteomics and metabolomics in the development of personalized treatment strategies would be also highlighted as a key area of research.

Furthermore, the special issue addresses the challenges and opportunities associated with immunotherapy, including the management of immune-related adverse events, mechanisms of resistance, strategies for overcoming immunosuppression within the tumor microenvironment, and potency assessment of therapeutic approaches.

Dr. Satoko Matsueda
Dr. Yoshimi Arima
Guest Editors

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Keywords

immunotherapy
personalized medicine
pharmacology study
toxicology study
immune-related adverse events
tumor microenvironment
immune escape
neoantigens
immune profiling
potency assessment
biomarker
combination therapy
tumor biology
molecular biology
molecular pathology

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Published Papers (7 papers)

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Research

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19 pages, 2133 KiB

Open AccessArticle

Prognostic Significance of Plasma Neutrophil Extracellular Trap Levels in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

by Shun Horaguchi, Yoshiro Nakahara, Yuka Igarashi, Taku Kouro, Feifei Wei, Kenta Murotani, Seiichi Udagawa, Naoko Higashijima, Norikazu Matsuo, Shuji Murakami, Terufumi Kato, Tetsuro Kondo, Huihui Xiang, Rika Kasajima, Hidetomo Himuro, Kayoko Tsuji, Yasunobu Mano, Mitsuru Komahashi, Yohei Miyagi, Haruhiro Saito, Koichi Azuma, Shuichiro Uehara and Tetsuro Sasada Show full author list Hide full author list

Biomedicines 2024, 12(8), 1831; https://doi.org/10.3390/biomedicines12081831 - 12 Aug 2024

Viewed by 1078

Abstract

Neutrophil extracellular traps (NETs) released from neutrophils are related to cancer progression. However, the relationship between the therapeutic effects of immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-PD-L1 antibodies and plasma NET concentration in patients with non-small cell lung cancer (NSCLC) is poorly understood. In this study, concentrations of citrullinated histone H3 (CitH3), a surrogate marker of NETs, in plasma before/after treatment were examined in patients with advanced or recurrent NSCLC undergoing ICI treatment (n = 185). The clinical significances of NET levels before/after treatment and posttreatment changes were statistically evaluated. As a result, multivariate Cox analysis showed that high NET levels before treatment were statistically significant predictors of unfavorable overall survival (OS; p < 0.001, HR 1.702, 95% CI 1.356–2.137) and progression-free survival (PFS; p < 0.001, HR 1.566, 95% CI 1.323–1.855). The Kaplan-Meier curves showed significant separation between the high- and low-NET groups in OS (p = 0.002) and PFS (p < 0.001). Additionally, high NET levels after treatment were also significantly associated with worse OS (p < 0.001) and PFS (p < 0.001) by multivariate Cox analysis. Notably, the pretreatment NET levels were significantly correlated with the plasma levels of NET-related inflammatory cytokines, such as IL-6 and IL-8, and with NET-related gene expression and immune-suppressive profile in peripheral blood mononuclear cells. Our findings suggest that NETs released from activated neutrophils might reduce the clinical efficacy of ICIs in patients with NSCLC. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

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12 pages, 273 KiB

Open AccessArticle

Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series

by Luigi Liguori, Angelo Luciano, Giovanna Polcaro, Alessandro Ottaiano, Marco Cascella, Francesco Perri, Stefano Pepe and Francesco Sabbatino

Biomedicines 2023, 11(11), 2974; https://doi.org/10.3390/biomedicines11112974 - 4 Nov 2023

Cited by 2 | Viewed by 1179

Abstract

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) have revolutionized the management of many types of solid tumors, including metastatic renal cell carcinoma (mRCC). Both sequential and combinatorial therapeutic strategies utilizing anti-PD-1 monoclonal antibodies (mAbs) and anti-angiogenic tyrosine kinase inhibitors (TKIs) have demonstrated to improve the survival of patients with mRCC as compared to standard therapies. On the other hand, both ICIs and TKIs are well known to potentially cause thyroid disorder adverse events (TDAEs). However, in the context of sequential therapeutic strategy, it is not clear whether prior anti-angiogenic TKI may increase the risk and/or the severity of ICI-related TDAEs. In this work, by describing and analyzing a case series of mRCC patients treated sequentially with prior TKIs and then with ICIs, we investigated the role of prior anti-angiogenic TKI-based treatment as a potential predisposing factor to anti-PD-1-mediated recurrent TDAEs, as well as its potential impact on the clinical characteristics of nivolumab-mediated recurrent TDAEs. Fifty mRCC patients were included in the analysis. TKI-mediated TDAEs were reported in ten out of fifty patients. TKI-mediated TDAEs were characterized by hypothyroidism in all ten patients. Specifically, 40%, 40% and 20% of patients presented grade 1, 2 and 3 hypothyroidisms, respectively. Following tumor progression and during anti-PD-1 nivolumab treatment, five out of ten patients developed anti-PD-1 nivolumab-mediated recurrent TDAEs. Anti-PD-1 nivolumab-mediated recurrent TDAEs were characterized by an early transient phase of thyrotoxicosis and a late phase of hypothyroidism in all five patients. The TDAEs were grade 1 and 2 in four and one patients, respectively. Prior anti-angiogenic TKI did not modify the clinical characteristics of nivolumab-mediated recurrent TDAEs. However, all five patients required an increased dosage of levothyroxine replacement therapy. In conclusion, our work suggests that prior anti-angiogenic TKI-based treatment significantly increases the risk of ICI-mediated recurrent TDAEs in patients with mRCC without modifying their clinical characteristics. The most relevant effect for these patients is the need to increase the dosage of lifelong levothyroxine replacement therapy. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

11 pages, 246 KiB

Open AccessArticle

Multi-Center Real-World Outcomes of Nivolumab Plus Ipilimumab and Chemotherapy in Patients with Metastatic Non-Small-Cell Lung Cancer

by Walid Shalata, Alexander Yakobson, Yulia Dudnik, Forat Swaid, Mohammad Sheikh Ahmad, Ashraf Abu Jama, Ahron Yehonatan Cohen and Abed Agbarya

Biomedicines 2023, 11(9), 2438; https://doi.org/10.3390/biomedicines11092438 - 31 Aug 2023

Cited by 6 | Viewed by 2315

Abstract

Immune checkpoint inhibitors have become the standard of care in the treatment of metastatic non-small-cell lung cancer (NSCLC). The combination of nivolumab plus ipilimumab and chemotherapy has been shown to improve outcomes in terms of overall survival (OS) and progression-free survival (PFS). The aim of this study was to evaluate the outcomes of metastatic NSCLC treated in routine practice on the treatment regimen of the CheckMate 9LA protocol. Medical records of 58 patients treated at Soroka and Bnai Zion Medical Centers between May 2020 and February 2022 were analyzed. All patients were treated with a regimen of platinum-based chemotherapy combined with immunotherapy of nivolumab every three weeks and ipilimumab every 6 weeks. The patients received 2–3 cycles of chemotherapy according to the physician’s choice: platinum-based cisplatin or carboplatin with either pemetrexed or paclitaxel. The median PFS was 10.2 months, longer than that of the 9LA trial (6.7 months). Adenocarcinoma patients exhibited a higher median OS of 13.7 (range 5–33) months than squamous cell carcinoma (SCC) patients at 12.3 (5–20) months and PFS of 10.3 (4–33) months, while squamous cell carcinoma patients had a PFS of 9.2 (4–18) months. Patients whose programmed death ligand-1 (PD-L1) tumor expression level was ≥1% showed a higher median OS than those with PD-L1 expression of less than 1%. Treatment-related adverse events (TRAEs) were reported in 93.1% of patients, mostly grade 1 in severity. The first-line treatment of metastatic NSCLC patients in combination with nivolumab plus ipilimumab and chemotherapy can be given safely in routine clinical practice, with results comparable to those achieved in clinical trials of the regimen. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

Review

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19 pages, 1063 KiB

Open AccessReview

Extracellular Vesicles and Immune System Function: Exploring Novel Approaches to Colorectal Cancer Immunotherapy

by Antonio Biondi, Marco Vacante, Roberta Catania and Giuseppe Sangiorgio

Biomedicines 2024, 12(7), 1473; https://doi.org/10.3390/biomedicines12071473 - 3 Jul 2024

Cited by 1 | Viewed by 910

Abstract

This review explores the emerging role of extracellular vesicles (EVs) in modulating immune system function and their application in novel cancer immunotherapy strategies, with a focus on colorectal cancer (CRC). EVs, as carriers of bioactive molecules, have shown potential in enhancing immune responses and overcoming the limitations of traditional therapies. We discuss the biogenesis, types, and functional roles of immune cell-derived EVs, their interactions with cancer cells, and their implications in antitumor immunity. Challenges such as tumor heterogeneity and immune evasion are addressed, alongside the promising therapeutic prospects of EV-based strategies. This comprehensive analysis underscores the transformative potential of EVs in cancer treatment paradigms. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

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16 pages, 1067 KiB

Open AccessReview

Exploring the Potential of Humoral Immune Response to Commensal Bifidobacterium as a Biomarker for Human Health, including Both Malignant and Non-Malignant Diseases: A Perspective on Detection Strategies and Future Directions

by Kyogo Itoh and Satoko Matsueda

Biomedicines 2024, 12(4), 803; https://doi.org/10.3390/biomedicines12040803 - 4 Apr 2024

Cited by 1 | Viewed by 1621

Abstract

In this comprehensive review, we explore the pivotal role of commensal Bifidobacterium (c-BIF) as potent non-self-antigens through antigenic mimicry, along with exploring the potential of humoral immune responses for both malignant and non-malignant disease. c-BIF, a predominant component of the human gut microbiome encompassing around 90% of the human genome, has emerged as a pivotal player in human biology. Over recent decades, there has been extensive research elucidating the intricate connections between c-BIF and various facets of human health, with particular emphasis on their groundbreaking impact on anti-cancer effects and the management of non-malignant diseases. The multifaceted role of c-BIF is explored, ranging from enhancing anti-tumor immunity to improving the efficacy of anti-cancer and anti-infectious disease strategies, and serving as predictive biomarkers for various diseases. Recent studies highlight not only c-BIF’s promotion of anti-tumor immunity but also their role in enhancing the efficacy of immune checkpoint inhibitors. The review emphasizes the promising avenue of manipulating the gut microbiota, particularly c-BIF, for modulating cancer immunotherapy with targeted effects on tumor cells while minimizing harm to normal tissue. In the context of infectious and inflammatory diseases, the crucial role of c-BIFs in the management of COVID-19 symptoms is examined, emphasizing their impact on the severity of and immune response to COVID-19. Furthermore, c-BIF exhibits preventive and therapeutic effects on Human Papillomaviruses (HPV) and shows promise in improving inflammatory bowel diseases. The potential application of c-BIF as a biomarker for immunotherapy is explored, with a specific emphasis on its predictive and prognostic value in cancer. Suggestions are made regarding the use of humoral immune responses to cytotoxic T lymphocyte (CTL) epitope peptides that share motifs with c-BIF, proposing them as potential markers for predicting overall survival in diverse cancer patients. In conclusion, c-BIF emerges as a crucial and multifaceted determinant of human health, across anti-tumor immunity to infectious and inflammatory disease management. The manipulation of c-BIF and gut microbiota presents a promising avenue for advancing therapeutic strategies, particularly in the realm of cancer immunotherapy. Additionally, this review highlights the significance of c-BIF as potent non-self-antigens via antigenic mimicry, emphasizing the importance of robust humoral immune responses against c-BIF for preventing various diseases, including inflammatory conditions. Elevated levels of circulating antibodies against c-BIF in healthy individuals may serve as potential indicators of lower risks for malignant and non-malignant diseases. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

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13 pages, 970 KiB

Open AccessReview

Immunological Mechanisms behind Anti-PD-1/PD-L1 Immune Checkpoint Blockade: Intratumoral Reinvigoration or Systemic Induction?

by Zhikun Guo, Jiangnan Yu, Zihan Chen, Shuxian Chen and Lei Wang

Biomedicines 2024, 12(4), 764; https://doi.org/10.3390/biomedicines12040764 - 29 Mar 2024

Cited by 1 | Viewed by 1721

Abstract

Anti-PD-1/PD-L1 immune checkpoint blockade (ICB) has been widely used to treat many types of cancer. It is well established that PD-L1 expressing cancer cells could directly inhibit the cytotoxicity of PD-1⁺ T cells via PD-L1-PD-1 interaction. However, histological quantification of intratumoral PD-L1 expression provides limited predictive value and PD-L1 negative patients could still benefit from ICB treatment. Therefore, the current major clinical challenges are low objective response rate and unclear immunological mechanisms behind responding vs. non-responding patients. Here, we review recent studies highlighting the importance of longitudinal pre- and post-ICB treatment on patients with various types of solid tumor to elucidate the mechanisms behind ICB treatment. On one hand, ICB induces changes in the tumor microenvironment by reinvigorating intratumoral PD-1⁺ exhausted T cells (“releasing the brakes”). On the other hand, ICB can also affect systemic antitumor immunity in the tumor-draining lymph node to induce priming/activation of cancer specific T cells, which is evident by T cell clonal expansion/replacement in peripheral blood. These studies reveal that ICB treatment not only acts on the tumor microenvironment (“battlefield”) but also acts on immune organs (“training camp”) of patients with solid tumors. A deeper understanding of the immunological mechanisms behind ICB treatment will pave the way for further improvements in clinical response. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

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Other

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15 pages, 970 KiB

Open AccessSystematic Review

Efficacy and Safety of Atezolizumab as a PD-L1 Inhibitor in the Treatment of Cervical Cancer: A Systematic Review

by Milan Daniel Velimirovici, Catalin Vladut Ionut Feier, Razvan Constantin Vonica, Alaviana Monique Faur and Calin Muntean

Biomedicines 2024, 12(6), 1291; https://doi.org/10.3390/biomedicines12061291 - 11 Jun 2024

Cited by 1 | Viewed by 1353

Abstract

Background and objectives: The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of atezolizumab, examining its impact on survival outcomes, response rates, and safety measured by serious adverse events (SAEs). Materials and methods: A literature search was conducted using PubMed, Scopus, and Web of Science, focusing on articles published up to February 2024. The review followed the PRISMA guidelines and synthesized outcomes from four randomized trial studies involving atezolizumab administered at 1200 mg IV every three weeks, alone or in combination with chemoradiotherapy. Results: A total of 284 patients received atezolizumab, the majority being advanced stage cervical cancer (IVA-IVB). Median follow-up times ranged from 9 weeks to 32.9 months. It was found that combining atezolizumab with standard therapies extended median progression-free survival (PFS) from 10.4 to 13.7 months and overall survival (OS) from 22.8 to 32.1 months, according to the phase III trial. Monotherapy and initial treatment settings with atezolizumab also showed promising efficacy, with disease-free survival rates at 24 months reaching 79% compared to 52% with standard therapy alone. However, the treatment was associated with high rates of SAEs, reaching up to 79% in more intensive treatment combinations. Conclusions: Atezolizumab demonstrates significant potential in improving PFS and OS in patients with cervical cancer, supporting its inclusion as a first-line treatment option. Despite the efficacy benefits, the high incidence of SAEs necessitates careful patient selection and management strategies to mitigate risks. This systematic review supports the continued evaluation of atezolizumab in broader clinical trials to refine its therapeutic profile and safety measures in the context of cervical cancer treatment. Full article

(This article belongs to the Special Issue Recent Advances in Immunotherapy for Solid Tumors)

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