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Cancer Immunotherapy: Current Advancements and Future Perspectives
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Cancer Immunotherapy: Current Advancements and Future Perspectives

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Methodology, Drug and Device Discovery".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 9987

Special Issue Editors

Dr. Stefano Forte

E-Mail Website
Guest Editor
Istituto Oncologico del Mediterraneo, 95029 Viagrande, Italy
Interests: experimental oncology; in vitro model of cancer; experimental radiotherapy in vitro and in vivo; cancer genomics
Special Issues, Collections and Topics in MDPI journals
Dr. Gianluca Ferini

E-Mail Website
Guest Editor
REM Radioterapia, 95029 Viagrande, Italy
Interests: experimental oncology

Special Issue Information

Dear Colleagues,

Even if target therapy has been conceived to dramatically improve the therapeutic outcomes in oncology, the real-life impact of this approach is still limited when considering its actual efficacy in tumor eradication. Complete and sustained long-term responses to anticancer therapies represent minority events in the vast therapeutic scenario in oncology, especially for some cancers such as melanoma, breast cancer, or brain tumors. The goal of immune therapy is to elicit and maintain an immune mediation response to cancer cells to establish a self-sustained process. For some specific applications, this approach demonstrates its significant effectiveness in diseases where therapeutic options are not particularly effective. Promising results have already been achieved in melanoma, non-small cell lung cancer, Hodgkin's lymphoma, and renal cell carcinoma. Other encouraging data are available for breast and bladder cancers and some myelomas and lymphomas. Unfortunately, the percentage of patients who benefit from these treatments remains limited, underlining the need to identify useful predictive features for their use. Several useful parameters have been considered to direct this therapeutic strategy, including the PD-L1 expression, lymphocytic infiltration, tumor mutational burden, microsatellites instability, and tumor inflammation signature. Regarding radiotherapy, it is well-known that it can induce abscopal and bystander effects by recruiting immune cells against the tumor. Unfortunately, such responses are episodic and not systematically inducible. These may be synergized and promoted by immunotherapy. Cutting-edge discoveries in this field explain the underlying cellular cascades that are waited for methodically to trigger these dramatic events in metastatic cancer patients. Modulating the radiation dose in terms of both size (such as in stereotactic body radiation therapy) and spatial delivery pattern (such as in the various spatially fractionated radiation therapy forms) is supposed to be a key factor to engage these off-target effects. Bench-to-bedside and vice versa findings are welcome in this Special Issue to shed light on the rationale and mechanisms of these new therapeutic opportunities.

The challenge is, therefore, to be able to develop immunotherapeutic strategies that meet the criteria of tolerability, manageability, efficacy, and that are economically sustainable. The weapon of immunotherapy should be made effective for a larger number of patients. It is also important to effectively combine immunotherapy with chemotherapy, radiotherapy or targeted therapies aiming towards a complete and sustainable disease eradication.

Dr. Stefano Forte
Dr. Gianluca Ferini
Guest Editors

Manuscript Submission Information

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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. Journal of Personalized Medicine is an international peer-reviewed open access monthly 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 2600 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

  • personalized immunotherapy
  • molecular pathways in cancer immunotherapy
  • precision medicine
  • molecular markers
  • molecular bases of abscopal effect
  • sustained therapeutic response

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Published Papers (6 papers)

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Research

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7 pages, 213 KiB  
Communication
The Role of Stereotactic Body Radiotherapy (SBRT) in Oligoprogressive Renal Cell Carcinoma (RCC) Treated with ICIs–TKIs: A Retrospective Multicentric Study
by Maria La Vecchia, Manuela Federico, Dario Aiello, Valentina Zagardo, Antonella Mazzonello, Lorella Testa, Leonarda La Paglia, Tiziana Bruno and Ivan Fazio
J. Pers. Med. 2024, 14(10), 1030; https://doi.org/10.3390/jpm14101030 - 27 Sep 2024
Viewed by 700
Abstract
Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine–kinase inhibitor (TKI). Methods: We retrospectively [...] Read more.
Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine–kinase inhibitor (TKI). Methods: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI–TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6–12–18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety. Results: After a median follow-up of 24 months, 6–12–18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded. Conclusions: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs–TKIs combination and SBRT upon oligoprogressive sites in mRCC. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)
9 pages, 1424 KiB  
Article
The Immunomodulatory Potential of Concurrent High-Dose Radiotherapy and Immune Checkpoint Inhibitor Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Initial Results
by Maria Chiara Lo Greco, Giorgia Marano, Roberto Milazzotto, Rocco Luca Emanuele Liardo, Irene Finocchiaro, Madalina La Rocca, Antonio Basile, Pietro Valerio Foti, Stefano Palmucci, Emanuele David, Stefano Pergolizzi and Corrado Spatola
J. Pers. Med. 2024, 14(6), 581; https://doi.org/10.3390/jpm14060581 - 29 May 2024
Cited by 1 | Viewed by 911
Abstract
In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary [...] Read more.
In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)
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13 pages, 1196 KiB  
Communication
Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?
by Gianluca Ferini, Valentina Zagardo, Paola Critelli, Anna Santacaterina, Serena Sava, Mandara Muralidhar Harikar, Tejas Venkataram, Giuseppe Emmanuele Umana, Anna Viola, Vito Valenti and Stefano Forte
J. Pers. Med. 2023, 13(5), 841; https://doi.org/10.3390/jpm13050841 - 17 May 2023
Cited by 2 | Viewed by 2015
Abstract
Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression [...] Read more.
Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab. Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively. Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy. Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)
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Review

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14 pages, 1052 KiB  
Review
Modulation of Radiation Doses and Chimeric Antigen Receptor T Cells: A Promising New Weapon in Solid Tumors—A Narrative Review
by Antonio Pontoriero, Paola Critelli, Federico Chillari, Giacomo Ferrantelli, Miriam Sciacca, Anna Brogna, Silvana Parisi and Stefano Pergolizzi
J. Pers. Med. 2023, 13(8), 1261; https://doi.org/10.3390/jpm13081261 - 14 Aug 2023
Cited by 4 | Viewed by 1763
Abstract
Tumor behavior is determined by its interaction with the tumor microenvironment (TME). Chimeric antigen receptor (CART) cell therapy represents a new form of cellular immunotherapy (IT). Immune cells present a different sensitivity to radiation therapy (RT). RT can affect tumor cells both modifying [...] Read more.
Tumor behavior is determined by its interaction with the tumor microenvironment (TME). Chimeric antigen receptor (CART) cell therapy represents a new form of cellular immunotherapy (IT). Immune cells present a different sensitivity to radiation therapy (RT). RT can affect tumor cells both modifying the TME and inducing DNA damage, with different effects depending on the low and high doses delivered, and can favor the expression of CART cells. CART cells are patients’ T cells genetically engineered to recognize surface structure and to eradicate cancer cells. High-dose radiation therapy (HDRT, >10–20 Gy/fractions) converts immunologically “cold” tumors into “hot” ones by inducing necrosis and massive inflammation and death. LDRT (low-dose radiation therapy, >5–10 Gy/fractions) increases the expansion of CART cells and leads to non-immunogenetic death. An innovative approach, defined as the LATTICE technique, combines a high dose in higher FDG- uptake areas and a low dose to the tumor periphery. The association of RT and immune checkpoint inhibitors increases tumor immunogenicity and immune response both in irradiated and non-irradiated sites. The aim of this narrative review is to clarify the knowledge, to date, on CART cell therapy and its possible association with radiation therapy in solid tumors. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)
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9 pages, 255 KiB  
Review
The Role of Radiotherapy in the Management of Vaginal Melanoma: A Literature Review with a Focus on the Potential Synergistic Role of Immunotherapy
by Francesco Cuccia, Salvatore D’Alessandro, Livio Blasi, Vito Chiantera and Giuseppe Ferrera
J. Pers. Med. 2023, 13(7), 1142; https://doi.org/10.3390/jpm13071142 - 16 Jul 2023
Cited by 5 | Viewed by 1957
Abstract
Among the mucosal melanomas, vaginal melanomas are very rare tumors, accounting for less than 20% of melanomas arising from the female genital tract. They occur most frequently in women in post-menopausal age, but younger patients may also experience this neoplasm, mainly located in [...] Read more.
Among the mucosal melanomas, vaginal melanomas are very rare tumors, accounting for less than 20% of melanomas arising from the female genital tract. They occur most frequently in women in post-menopausal age, but younger patients may also experience this neoplasm, mainly located in the lower third of the vagina or the anterior wall. The optimal management of this tumor remains controversial, with surgery reported as the most frequently adopted approach. However, a clear benefit of surgical treatment in terms of survival has not yet been demonstrated. Conversely, radiotherapy may represent an attractive non-invasive alternative, and there are several favorable reports of the role of radiation therapy, either delivered with photons, brachytherapy, or hadrontherapy. A wide range of techniques and fractionation regimens are reported with substantially good tolerance to the treatment, and acute G3 or higher toxicities are reported only in the case of concurrent immunotherapy. Of note, due to the rarity of the disease, there is a lack of high-level evidence for the optimal therapeutic option. In this scenario, recent studies theorize the possibility of developing combinatorial approaches of radiotherapy with immunotherapy based on cutaneous melanomas reports. In this review, we aim to summarize the evidence available in the literature supporting the role of definitive radiotherapy for vaginal melanomas, with a focus on the combination of RT with immunotherapy, in terms of optimal timing and biological rationale. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)

Other

Jump to: Research, Review

9 pages, 4963 KiB  
Case Report
Unexpected Transient Glioblastoma Regression in a Patient Previously Treated with Bacillus Calmette–Guérin Therapy: A Case Report and Immunomodulatory Effects Hypothesis
by Gianluca Scalia, Gianluca Ferini, Salvatore Marrone, Maurizio Salvati, Vicky Yamamoto, Babak Kateb, Reinhard Schulte, Stefano Forte and Giuseppe Emmanuele Umana
J. Pers. Med. 2023, 13(12), 1661; https://doi.org/10.3390/jpm13121661 - 28 Nov 2023
Cited by 2 | Viewed by 1246
Abstract
(1) Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has been used as an immunotherapeutic agent in bladder cancer and has shown non-specific beneficial [...] Read more.
(1) Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Bacillus Calmette–Guérin (BCG), a live attenuated strain of Mycobacterium bovis, has been used as an immunotherapeutic agent in bladder cancer and has shown non-specific beneficial effects. This report presents a unique case of GBM regression following BCG therapy for bladder cancer, suggesting the potential systemic immunomodulatory effects of BCG on GBM. (2) Case Presentation: A 67-year-old male with a history of bladder cancer treated with BCG presented with neurological symptoms. Imaging revealed two GBM lesions, and surgery was performed to remove one. Subsequently, the patient experienced complete tumor regression after initial stability. (3) Conclusions: This case highlights the potential of BCG or other immunotherapies in GBM treatment and underscores the need for further research. Understanding the immunomodulatory effects of BCG on GBM could lead to innovative therapies for this devastating disease; although, overcoming the immune evasion mechanisms in the brain is a significant challenge. Further investigation is warranted to explore this promising avenue of research. Full article
(This article belongs to the Special Issue Cancer Immunotherapy: Current Advancements and Future Perspectives)
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