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Cancers
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Evidence from the Real World Provides New Insights into the...
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Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy

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

Deadline for manuscript submissions: 30 April 2025 | Viewed by 10224

Special Issue Editors

Dr. Fabrizio Nelli

E-Mail Website
Guest Editor
Medical Oncology Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, 01100 Viterbo, Italy
Interests: thoracic malignancies; immunotherapy; real-world outcome research; biomarkers
Dr. Carlo Signorelli

E-Mail Website
Guest Editor
Medical Oncology Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, 01100 Viterbo, Italy
Interests: gastrointestinal malignancies; immunotherapy; real-world outcome research; biomarkers
Dr. Enzo Ruggeri

E-Mail Website
Guest Editor
Medical Oncology Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, 01100 Viterbo, Italy
Interests: genitourinary malignancies; head and neck malignancies; immunotherapy; real-world outcome research; biomarkers

Special Issue Information

Dear Colleagues,

Immunotherapy has profoundly changed the therapeutic landscape for many types of solid cancer. While we are witnessing the introduction of novel immune checkpoint inhibitors and combination regimens into clinical practice, as well as expanded therapeutic indications, several controversies still remain to be addressed. Real-world studies have proven valuable as they bridge the gap between clinical trials and routine practice, shedding light on issues that would otherwise be difficult to examine through prospective research. These include, but are not limited to, challenges related to concurrent loco-regional treatments or arising from the concomitant use of medications required for relevant comorbidities or to support cytotoxic and targeted therapies. This Special Issue of Cancers aims to showcase new research articles and timely reviews on the management of clinical practice issues during immune checkpoint blockade in solid malignancies.

Dr. Fabrizio Nelli
Dr. Carlo Signorelli
Dr. Enzo Ruggeri
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

  • immune-checkpoint inhibitors
  • solid tumors
  • cytotoxic chemotherapy
  • targeted therapies
  • radiotherapy
  • concomitants medications
  • supportive therapies
  • real-world investigation

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Published Papers (5 papers)

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Research

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12 pages, 930 KiB  
Article
The Significance of Longitudinal Psoas Muscle Loss in Predicting the Maintenance Efficacy of Durvalumab Treatment Following Concurrent Chemoradiotherapy in Patients with Non-Small Cell Lung Cancer: A Retrospective Study
by Haruka Kuno, Naoya Nishioka, Tadaaki Yamada, Yusuke Kunimatsu, Akihiro Yoshimura, Soichi Hirai, Shun Futamura, Taiki Masui, Masashi Egami, Yusuke Chihara and Koichi Takayama
Cancers 2024, 16(17), 3037; https://doi.org/10.3390/cancers16173037 - 30 Aug 2024
Viewed by 969
Abstract
Sarcopenia assessed at a single time point is associated with the efficacy of immunotherapy, and we hypothesized that longitudinal changes in muscle mass may also be important. This retrospective study included patients with non-small cell lung cancer (NSCLC) who received durvalumab treatment after [...] Read more.
Sarcopenia assessed at a single time point is associated with the efficacy of immunotherapy, and we hypothesized that longitudinal changes in muscle mass may also be important. This retrospective study included patients with non-small cell lung cancer (NSCLC) who received durvalumab treatment after concurrent chemoradiotherapy (CCRT) between January 2017 and April 2023. Muscle loss and sarcopenia were assessed based on the lumbar skeletal muscle area. Patients with a decrease in muscle area of 10% or more during CCRT were categorized into the muscle loss group, while those with a decrease of less than 10% were categorized into the muscle maintenance group. We evaluated the relationship between muscle changes during CCRT and the efficacy of durvalumab treatment. Among the 98 patients, the muscle maintenance group had a significantly longer PFS of durvalumab treatment compared to the muscle loss group (29.2 months [95% confidence interval (CI): 17.2—not reached] versus 11.3 months [95% CI: 7.6–22.3]; p = 0.008). The multivariable analysis confirmed that muscle change was a significant predictor of a superior PFS (HR: 0.47 [95% CI: 0.25–0.90]; the p-value was less than 0.05). In contrast, the OS between the groups did not differ significantly (not reached [95% CI: 21.8 months—not reached] and 36.6 months [95% CI: 26.9—not reached]; p = 0.49). Longitudinal muscle changes during CCRT are a predictor of durvalumab’s efficacy in patients with NSCLC after CCRT. Full article
(This article belongs to the Special Issue Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy)
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19 pages, 994 KiB  
Article
Real-World Safety and Outcome of First-Line Pembrolizumab Monotherapy for Metastatic NSCLC with PDL-1 Expression ≥ 50%: A National Italian Multicentric Cohort (“PEMBROREAL” Study)
by Alessandro Cafaro, Flavia Foca, Oriana Nanni, Marco Chiumente, Marina Coppola, Alberto Russi, Elena Svegliati, Paolo Baldo, Sabrina Orzetti, Fiorenza Enrico, Federico Foglio, Davide Pinnavaia, Vito Ladisa, Claudia Lauria Pantano, Rosa Lerose, Patrizia Nardulli, Simona Ferraiuolo, Piera Maiolino, Immacolata De Stasio, Federica Gradellini, Anna Rita Gasbarro, Rossella Santeramo, Gisella Carrucciu, Riccardo Provasi, Mario Cirino, Paola Cristina Cappelletto, Elisabetta Fonzi, Alessandra Pasqualini, Stefano Vecchia, Marianna Veraldi, Adele Emanuela De Francesco, Lucio Crinò, Angelo Delmonte and Carla Masiniadd Show full author list remove Hide full author list
Cancers 2024, 16(10), 1802; https://doi.org/10.3390/cancers16101802 - 8 May 2024
Cited by 2 | Viewed by 2344
Abstract
Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine [...] Read more.
Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan–Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6–10.0) and 25.5 months (95% CI: 21.8–31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution. Full article
(This article belongs to the Special Issue Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy)
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Review

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16 pages, 920 KiB  
Review
The Current State of the Diagnoses and Treatments for Clear Cell Renal Cell Carcinoma
by Anthony E. Quinn, Scott D. Bell, Austin J. Marrah, Mark R. Wakefield and Yujiang Fang
Cancers 2024, 16(23), 4034; https://doi.org/10.3390/cancers16234034 - 1 Dec 2024
Viewed by 1571
Abstract
Clear cell renal cell carcinoma is the most common form of kidney cancer, accounting for 75% of malignant kidney tumors, and is generally associated with poor patient outcomes. With risk factors including smoking, obesity, and hypertension, all of which have a high prevalence [...] Read more.
Clear cell renal cell carcinoma is the most common form of kidney cancer, accounting for 75% of malignant kidney tumors, and is generally associated with poor patient outcomes. With risk factors including smoking, obesity, and hypertension, all of which have a high prevalence in the United States and Europe, as well as genetic factors including tuberous sclerosis complex and Von Hippel–Lindau syndrome, there is an increasing need to expand our present understanding. The current clear cell renal cell carcinoma knowledge is outdated, with obsolete diagnostic criteria and moderately invasive surgical treatments still prevailing, partially ascribed to its resistance to chemotherapy and radiation therapy. The standard of treatment relies on surgical intervention, including radical nephrectomy and partial nephrectomy, while more recent treatments target neoplastic growth pathways and immune regulation checkpoints. Full article
(This article belongs to the Special Issue Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy)
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17 pages, 1522 KiB  
Review
Into the Future: Fighting Melanoma with Immunity
by Derek A. Corica, Scott D. Bell, Peyton J. Miller, Daniel T. Kasperbauer, Nicholas J. Lawler, Mark R. Wakefield and Yujiang Fang
Cancers 2024, 16(23), 4002; https://doi.org/10.3390/cancers16234002 - 29 Nov 2024
Viewed by 966
Abstract
Immunotherapy offers a novel and promising option in the treatment of late-stage melanoma. By utilizing the immune system to assist in tumor destruction, patients have additional options after tumor progression. Immune checkpoint inhibitors reduce the ability for tumors to evade the immune system [...] Read more.
Immunotherapy offers a novel and promising option in the treatment of late-stage melanoma. By utilizing the immune system to assist in tumor destruction, patients have additional options after tumor progression. Immune checkpoint inhibitors reduce the ability for tumors to evade the immune system by inhibiting key surface proteins used to inactivate T-cells. Without these surface proteins, T-cells can induce cytotoxic responses against tumors. Tumor infiltrating lymphocyte therapy is a form of adoptive cell therapy that takes advantage of a small subset of T-cells that recognize and infiltrate tumors. Isolation and rapid expansion of these colonies assist the immune system in mounting a charged response that can induce remission. Tumor vaccines deliver a high dose of unique antigens expressed by tumor cells to the entire body. The introduction of large quantities of tumor antigens upregulates antigen presenting cells and leads to effective activation of the immune system against tumors. Cytokine therapy introduces high amounts of chemical messengers that are endogenous to the immune system and support T-cell expansion. While other methods of immunotherapy exist, immune checkpoint inhibitors, tumor infiltrating lymphocytes, tumor vaccines, and cytokine therapy are commonly used to treat melanoma. Like many other cancer treatments, immunotherapy is not without adverse effects, as toxicities represent a major obstacle. However, immunotherapy has been efficacious in the treatment of melanoma. Full article
(This article belongs to the Special Issue Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy)
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16 pages, 2077 KiB  
Review
Dendritic Cells in Shaping Anti-Tumor T Cell Response
by Luciano Mazzoccoli and Bei Liu
Cancers 2024, 16(12), 2211; https://doi.org/10.3390/cancers16122211 - 13 Jun 2024
Cited by 6 | Viewed by 3800
Abstract
Among professional antigen-presenting cells, dendritic cells (DCs) orchestrate innate and adaptive immunity and play a pivotal role in anti-tumor immunity. DCs are a heterogeneous population with varying functions in the tumor microenvironment (TME). Tumor-associated DCs differentiate developmentally and functionally into three main subsets: [...] Read more.
Among professional antigen-presenting cells, dendritic cells (DCs) orchestrate innate and adaptive immunity and play a pivotal role in anti-tumor immunity. DCs are a heterogeneous population with varying functions in the tumor microenvironment (TME). Tumor-associated DCs differentiate developmentally and functionally into three main subsets: conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (MoDCs). There are two major subsets of cDCs in TME, cDC1 and cDC2. cDC1 is critical for cross-presenting tumor antigens to activate cytotoxic CD8+ T cells and is also required for priming earlier CD4+ T cells in certain solid tumors. cDC2 is vital for priming anti-tumor CD4+ T cells in multiple tumor models. pDC is a unique subset of DCs and produces type I IFN through TLR7 and TLR9. Studies have shown that pDCs are related to immunosuppression in the TME through the secretion of immunosuppressive cytokines and by promoting regulatory T cells. MoDCs differentiate separately from monocytes in response to inflammatory cues and infection. Also, MoDCs can cross-prime CD8+ T cells. In this review, we summarize the subsets and functions of DCs. We also discuss the role of different DC subsets in shaping T cell immunity in TME and targeting DCs for potential immunotherapeutic benefits against cancer. Full article
(This article belongs to the Special Issue Evidence from the Real World Provides New Insights into the Evolving Landscape of Cancer Immunotherapy)
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