Immunotherapy against Tumors: Light and Darkness

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 9730

Special Issue Editors


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Guest Editor
Scientific Direction, Candiolo Cancer Institute (FPO-IRCCS), Candiolo, Italy
Interests: head and neck cancer; immunotherapy; translational research
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Azienda Ospedaliera S. Croce e Carle Cuneo, 12100 Cuneo, Italy
Interests: breast cancer; translational research; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Immunotherapy represents a revolutionary advancement in cancer management. Unbelievable developments in tumors which were historically resistant to conventional systemic therapies are reported every year during the major international cancer conferences. This justifies the enthusiasm with which immunotherapy has been met since the first presentation of ipilimumab in metastatic malignant melanoma more than a decade ago. 

However, we are still only using one class of immune agent: immune checkpoint inhibitors (ICIs), namely anti-PD-(L)1 and anti-CTLA-4. New drugs directed against different immune targets struggle to prove their clinical usefulness, although they have not yet been abandoned. In addition, notwithstanding the excellent results achieved, the majority of patients do not benefit from ICIs, and their combination (Anti-PD-(L)1 + Anti-CTLA-4) is showing even fewer positive results. 

Two different mechanisms underlie immunotherapy failures: firstly, primary resistance, due to the tumor microenvironment that changes between tumors of different origins and also within each cancer type, leading to different escape mechanisms; and secondly, acquired resistance, i.e., the upregulation of redundant mechanisms that occur when the main one is chronically inhibited. 

This awareness should lead to two lines of research on immunotherapy, the first dedicated to identifying the tumor microenvironment of each patient, and the second to the prevention and treatment of acquired resistance mechanisms. The goal is to lead us to a more conscious use of immunotherapy, better selecting the patients to be treated, and with which drug. In this perspective, even drugs currently abandoned, in addition to those under development, will be able to show their real value. Furthermore, a better understanding of resistance mechanisms paves the way to a rational combination of immunotherapy and conventional therapies. 

This Special issue is focused on the recent scientific progresses achieved in this field. Based on your extensive knowledge and experience, we invite you to contribute with an original report, original observation or review, to summarize the state of the art of immunotherapy in solid tumors and highlight the future potential usefulness of knowledge of their microenvironment, the ongoing research to identify the specific mechanisms of primary and secondary escape, new drugs in development, and new approaches, such as CAR-T, CAR-NK, and cytokine-activated killer cells.

Dr. Marco Carlo Merlano
Dr. Ornella Garrone
Guest Editor

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Keywords

  • immunotherapy
  • mechanisms of resistance
  • tumor microenvironment
  • new immunotherapy treatments

Published Papers (4 papers)

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8 pages, 238 KiB  
Article
New Challenges in Evaluating Outcomes after Immunotherapy in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
by Andrea Alberti, Luigi Lorini, Marco Ravanelli, Francesco Perri, Marie Vinches, Paolo Rondi, Chiara Romani and Paolo Bossi
Vaccines 2022, 10(6), 885; https://doi.org/10.3390/vaccines10060885 - 1 Jun 2022
Cited by 3 | Viewed by 1764
Abstract
In many recurrent and/or metastatic cancers, the advent of immunotherapy opens up new scenarios of treatment response, with new phenomena, such as pseudoprogression and hyperprogression. Because of this, different immune-related response criteria have been developed, and new therapeutic strategies adopted, such as treatment [...] Read more.
In many recurrent and/or metastatic cancers, the advent of immunotherapy opens up new scenarios of treatment response, with new phenomena, such as pseudoprogression and hyperprogression. Because of this, different immune-related response criteria have been developed, and new therapeutic strategies adopted, such as treatment beyond progression. Moreover, the role of progression-free survival as a surrogate has been questioned, and new surrogate endpoint hypotheses have arisen. A proper understanding of radiological imaging, an assessment of the biological events triggered by therapy, and the clinical evolution of the lesions and of the patient performance status are all factors that should be considered to guide the oncologist’s treatment choice. The primary aim of this article is to discuss how all these concepts apply to recurrent/metastatic head and neck squamous cell carcinoma patients when treated with immunotherapy. Full article
(This article belongs to the Special Issue Immunotherapy against Tumors: Light and Darkness)
11 pages, 530 KiB  
Article
Renal Function Outcomes in Metastatic Non-Small-Cell Lung Carcinoma Patients Treated with Chemotherapy or Immune Checkpoint Inhibitors: An Unexpected Scenario
by Francesco Trevisani, Federico Di Marco, Matteo Floris, Antonello Pani, Roberto Minnei, Mario Scartozzi, Alessio Cirillo, Alain Gelibter, Andrea Botticelli, Erika Rijavec, Monica Cattaneo, Ornella Garrone and Michele Ghidini
Vaccines 2022, 10(5), 679; https://doi.org/10.3390/vaccines10050679 - 24 Apr 2022
Cited by 4 | Viewed by 2402
Abstract
Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are effective therapeutic agents for the palliative treatment of metastatic non-small-cell lung cancer (NSCLC); the aim of our study was to investigate the acute and chronic renal toxicities in this setting. We collected data on [...] Read more.
Immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy (CT) are effective therapeutic agents for the palliative treatment of metastatic non-small-cell lung cancer (NSCLC); the aim of our study was to investigate the acute and chronic renal toxicities in this setting. We collected data on 292 patients who received cisplatin (35%), carboplatin-based regimens (25%), or ICI monotherapy (40%). The primary and secondary outcomes were compared to the acute kidney injury (AKI) rate and the mean estimated GFR (eGFR) decay between groups, respectively, over a mean follow-up duration of 15 weeks. We observed 26 AKI events (8.9%), mostly stage I AKI (80.7%); 15% were stage II AKI, 3.8% were stage III, and none required renal replacement therapy or ICU admission. The AKI rates were 10.9%, 6.8%, and 8.9% for the cisplatin, carboplatin, and ICI groups, respectively, and no significant differences were observed between the groups (p = 0.3). A global mean eGFR decay of 2.2 mL/min was observed, while for the cisplatin, carboplatin, and ICI groups, the eGFR decay values were 2.3 mL/min, 1.1 mL/min, and 3.5 mL/min, respectively. No significant differences were observed between the groups. Cisplatin/carboplatin-based CT and ICIs resulted in a similar incidence of AKI and eGFR decay, suggesting the safety of their cautious use, even in CKD patients. Full article
(This article belongs to the Special Issue Immunotherapy against Tumors: Light and Darkness)
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18 pages, 2581 KiB  
Article
Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression
by Matteo Paccagnella, Andrea Abbona, Andrea Michelotti, Elena Geuna, Fiorella Ruatta, Elisabetta Landucci, Nerina Denaro, Paola Vanella, Cristiana Lo Nigro, Danilo Galizia, Marco Merlano and Ornella Garrone
Vaccines 2022, 10(1), 78; https://doi.org/10.3390/vaccines10010078 - 5 Jan 2022
Cited by 13 | Viewed by 2210
Abstract
Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with [...] Read more.
Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome. We evaluated 18 cytokines in breast cancer patients treated with eribulin before starting treatment (T0) and after four courses of therapy (T1). Longitudinal modifications were considered and cytokine clusters through PCA and HCPC correlated to patients’ outcomes were identified. Forty-one metastatic breast cancer patients and fifteen healthy volunteers were included. After clustering, we identified at T0 six patient clusters with different risk of relapse and death. At T1, only four clusters were identified, and three of them accounted for thirty-eight of forty-one patients, suggesting a possible role of treatment in reducing heterogeneity. The cluster with the best survival at T1 was characterized by low levels of IL-4, IL-6, IL-8, IL-10, CCL-2, CCL-4, and TGF-β. The cluster showing the worst survival encompassed high levels of IL-4, IL-6, IL-8, IL-10, CCL-2, and IFN-γ. A subgroup of patients with short progression-free survival (PFS) and long overall survival (OS) was comprised in the cluster characterized by low levels of CCL-2, IL-6, IL-8, IL-10, and IL-12 at T0. Our data support the prognostic significance of longitudinal serum cytokine analysis. This approach may help identify patients for whom early treatment stop avoids needless toxicity or might justify treatment beyond early progression. Further investigations are required to validate this hypothesis. Full article
(This article belongs to the Special Issue Immunotherapy against Tumors: Light and Darkness)
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14 pages, 2642 KiB  
Systematic Review
Resistance Mechanisms Influencing Oncolytic Virotherapy, a Systematic Analysis
by Darshak K. Bhatt, Roger Chammas and Toos Daemen
Vaccines 2021, 9(10), 1166; https://doi.org/10.3390/vaccines9101166 - 12 Oct 2021
Cited by 14 | Viewed by 2756
Abstract
Resistance to therapy is a frequently observed phenomenon in the treatment of cancer, and as with other cancer therapeutics, therapies based on oncolytic viruses also face the challenges of resistance, such as humoral and cellular antiviral responses, and tumor-associated interferon-mediated resistance. In order [...] Read more.
Resistance to therapy is a frequently observed phenomenon in the treatment of cancer, and as with other cancer therapeutics, therapies based on oncolytic viruses also face the challenges of resistance, such as humoral and cellular antiviral responses, and tumor-associated interferon-mediated resistance. In order to identify additional mechanisms of resistance that may contribute to therapeutic failure, we developed a systematic search strategy for studies published in PubMed. We analyzed 6143 articles on oncolytic virotherapy and found that approximately 8% of these articles use resistance terms in the abstract and/or title. Of these 439 articles, 87 were original research. Most of the findings reported pertain to resistance mediated by tumor-cell-dependent interferon signaling. Yet, mechanisms such as epigenetic modifications, hypoxia-mediated inhibition, APOBEC-mediated resistance, virus entry barriers, and spatiotemporal restriction to viral spread, although not frequently assessed, were demonstrated to play a major role in resistance. Similarly, our results suggest that the stromal compartment consisting of, but not limited to, myeloid cells, fibroblasts, and epithelial cells requires more study in relation to therapy resistance using oncolytic viruses. Thus, our findings emphasize the need to assess the stromal compartment and to identify novel mechanisms that play an important role in conferring resistance to oncolytic virotherapy. Full article
(This article belongs to the Special Issue Immunotherapy against Tumors: Light and Darkness)
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