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Cancers
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The Relationship of Cancer with Infection and the Immune System
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The Relationship of Cancer with Infection and the Immune System

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 6722

Special Issue Editor

Dr. Antonio Facchiano

E-Mail Website
Guest Editor
Laboratory of Molecular Oncology, Istituto Dermopatico dell’Immacolata, IDI-IRCCS, Rome, Italy
Interests: melanoma markers; angiogenic factors; melanoma therapy and diagnosis; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The role of the immune system in cancer development has been extensively investigated. It is well known that reciprocal recognition between T cells and cancer cells is a necessary but insufficient step in the immune reaction to cancer. Additionally, co-inhibitory and co-stimulatory reciprocal recognition steps have been identified and characterized, and are known to control the immune response to cancer cells. In this Special Issue, new data will be presented regarding mechanisms that control the immune response to melanoma and other skin cancers and that have led to innovative immunotherapy approaches. There will be a focus on: the identification/characterization of novel markers able to predict the response to therapy; the identification/characterization of novel immune check points; and the identification of previous or co-occurring infections affecting the immune response to skin-cancers. 

Full articles and reviews that address innovative aspects of skin cancer immunotherapy will be considered.

Dr. Antonio Facchiano
Guest Editor

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 system
  • T cells and cancer cells
  • immune response
  • melanoma
  • skin cancers
  • immunotherapy

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Published Papers (3 papers)

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Research

15 pages, 5102 KiB  
Article
TIL-Derived CAR T Cells Improve Immune Cell Infiltration and Survival in the Treatment of CD19-Humanized Mouse Colorectal Cancer
by Can Zhu, Yuanyuan Zhao, Jiaheng He, Huan Zhao, Li Ni, Xinyi Cheng, Yida Chen, Liqian Mu, Xiaojun Zhou, Qin Shi and Jie Sun
Cancers 2023, 15(23), 5567; https://doi.org/10.3390/cancers15235567 - 24 Nov 2023
Cited by 3 | Viewed by 2547
Abstract
Chimeric antigen receptor-engineered T cells (CAR Ts) targeting CD19 have shown unprecedented prognosis in treating hematological cancers. However, the lack of a tumor-specific antigen as the target and an inhospitable tumor environment limit the clinical application of CAR T in solid tumors. Tumor-infiltrating [...] Read more.
Chimeric antigen receptor-engineered T cells (CAR Ts) targeting CD19 have shown unprecedented prognosis in treating hematological cancers. However, the lack of a tumor-specific antigen as the target and an inhospitable tumor environment limit the clinical application of CAR T in solid tumors. Tumor-infiltrating T lymphocytes (TIL) exhibit diverse T cell receptor clonality and superior tumor-homing abilities. Therefore, in our study, human CD19-target TIL CAR-Ts armed with CD3ζ and 4-1BB signaling domains were constructed. Mouse colorectal cancer CT26 cells expressing human CD19 (hCD19+-CT26) were developed to assess the anti-tumor activity of TIL CAR-T cells, both in vitro and in vivo. Compared with splenic CAR T adoptive transfer, TIL CAR-T administration showed superior tumor suppression ability in hCD19+-CT26 tumor-bearing mice. Furthermore, more T cells were found at the tumor site and had lower exhaustion-related inhibitory receptor (T cell immunoglobulin and mucin domain-containing protein 3, Tim3) expression and higher immune memory molecule (CD62L) expression. Overall, we provided an artificial tumor-specific antigen in solid tumors and demonstrated that combined CAR-expressing TIL-Ts (TIL CAR-Ts) exhibited strong anti-tumor activity, with improved T cell infiltration and immune memory. Our humanized tumor antigen presented platform of mice suggests that TIL CAR-T-based adoptive therapy could be a promising strategy for solid cancer treatment. Full article
(This article belongs to the Special Issue The Relationship of Cancer with Infection and the Immune System)
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13 pages, 1492 KiB  
Article
Impact of Sepsis on the Oncologic Outcomes of Advanced Epithelial Ovarian Cancer Patients: A Multicenter Observational Study
by Sherin A. Said, Joanne A. de Hullu, Maaike A. van der Aa, Janneke E. W. Walraven, Ruud L. M. Bekkers, Brigitte F. M. Slangen, Peter Pickkers and Anne M. van Altena
Cancers 2023, 15(18), 4642; https://doi.org/10.3390/cancers15184642 - 20 Sep 2023
Cited by 1 | Viewed by 1485
Abstract
Objective: The sepsis-induced inflammatory response may potentially affect malignant cells. Recently, a case of spontaneous regression of a histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) following sepsis was reported. The aim of our study was [...] Read more.
Objective: The sepsis-induced inflammatory response may potentially affect malignant cells. Recently, a case of spontaneous regression of a histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) following sepsis was reported. The aim of our study was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Methods: Gynecologic oncologic patients admitted to the Intensive Care Unit of three oncologic centers between 2006 and 2019 were identified and patients who experienced sepsis following advanced-stage EOC diagnosis were selected. Survival outcomes were compared with advanced-stage EOC patients from the Netherlands Cancer Registry (NCR). To correct for case-mix differences, propensity score matching using 1:3 nearest neighbor matching was conducted after which survival analyses were repeated. Results: A total of 18 of 215 patients with advanced-stage EOC experienced sepsis. Sepsis patients had similar distributions of patient, tumor, and treatment characteristics to 3988 patients from the NCR cohort. A total of 3 of 18 patients died from the complications of sepsis. While the remaining patients initially responded to treatment, 14/15 patients relapsed. The median (IQR) overall survival was 31 (24–44) and 35 (20–60) months for the sepsis and unmatched NCR cohort (p = 0.56), respectively. The median (IQR) progression-free survival was 16 (11–21) and 16 (11–27) months (p = 0.90), respectively. Survival outcomes did not differ following propensity matching (overall survival of 31 (24–44) vs. 36 (20–56) months, p = 0.40; progression-free survival of 16 (11–21) and 16 (12–21) months, p = 0.72). Conclusion: In this observational study, the occurrence of sepsis did not affect the oncologic and survival outcomes of advanced-stage EOC patients. Full article
(This article belongs to the Special Issue The Relationship of Cancer with Infection and the Immune System)
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17 pages, 2334 KiB  
Article
Changes in Peripheral Immune Cells after the Third Dose of SARS-CoV-2 mRNA-BNT162b2 Vaccine and Disease Outcomes in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Prospective Analysis of the Vax-on-Third-Profile Study
by Fabrizio Nelli, Carlo Signorelli, Agnese Fabbri, Diana Giannarelli, Antonella Virtuoso, Julio Rodrigo Giron Berrios, Eleonora Marrucci, Cristina Fiore, Marta Schirripa, Mario Giovanni Chilelli, Francesca Primi, Valentina Panichi, Giuseppe Topini, Maria Assunta Silvestri and Enzo Maria Ruggeri
Cancers 2023, 15(14), 3625; https://doi.org/10.3390/cancers15143625 - 14 Jul 2023
Cited by 2 | Viewed by 2143
Abstract
Background: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade [...] Read more.
Background: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade are not fully understood. We conducted a prospective analysis of the Vax-On-Third-Profile study to evaluate the impact of circulating lymphocyte dynamics on disease outcomes in this subgroup of patients. Methods: Recipients of booster dosing who had received before vaccination at least one course of an anti-PD-1/PD-L1 treatment for an advanced solid tumor were eligible. Immunophenotyping of peripheral blood was performed before the third dose of tozinameran (timepoint-1) and four weeks later (timepoint-2) to quantify the absolute counts of lymphocyte subpopulations, including CD3+CD4+ T cells, CD3+CD8+ T cells, B cells, and NK cells. Logistic regression was used to analyze the relationship between lymphocyte subsets and durable clinical benefit (DCB). The log-rank test and Cox regression model were applied to evaluate the relationship between lymphocyte subpopulations and both vaccine-related time-to-treatment failure (V-TTF) and overall survival (OS). Results: We included a total of 56 patients with metastatic disease who were given a third dose of tozinameran between 23 September and 7 October 2021 (median age: 66 years; male: 71%). Most recipients had a diagnosis of lung cancer and were being treated with pembrolizumab or nivolumab. Compared to baseline, the third immunization resulted in an incremental change in the median counts of all lymphocyte subpopulations, which was statistically significant only for NK cells (p < 0.001). A significant correlation was found between NK cell counts and DCB at timepoint-2 (p < 0.001). Multivariate logistic regression analysis of DCB confirmed the predictive significance of high-level NK cell counts (p = 0.020). In multivariate Cox regression analysis, high-level NK cell counts independently predicted longer V-TTF [HR 0.34 (95% CI 0.14–0.80), p = 0.014] and OS [HR 0.36 (95% CI 0.15–0.89), p = 0.027]. Conclusions: Our data suggest expansion of NK cell counts as the most noteworthy change in circulating lymphocytes after the third dose of tozinameran in cancer patients receiving PD-1/PD-L1-targeted agents. This change correlated with enhanced therapeutic efficacy, improving the rate of disease control, and prolonging survival outcomes. Similar findings have not been previously reported, implying that they have proof-of-concept value and warrant further confirmation. Full article
(This article belongs to the Special Issue The Relationship of Cancer with Infection and the Immune System)
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