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Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 12701

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Special Issue Editors

Dr. Diletta Di Mitri

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Guest Editor

Unit of Advanced Optical Microscopy, Humanitas Clinical and Research Center – IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
Interests: innate immunity; tumor immunology; tumor microenvironment; tumor-associated macrophages; prostate cancer; immunotherapy; resistance to cancer therapy; high-dimensional profiling of immune subsets
Special Issues, Collections and Topics in MDPI journals

Dr. Marco Erreni

E-Mail Website
Guest Editor

Unit of Advanced Optical Microscopy, Humanitas Clinical and Research Center – IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy
Interests: tumor microenvironment; tumor-associated macrophages; colorectal cancer; inflammatory bowel diseases; cancer-related inflammation; innate immunity; optical imaging; intravital microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second volume of our previous Special Issue “Immune Response to Cancer: From Tumor Onset to Therapeutic Approach”. Cancer represents a major leading cause of death worldwide. In recent decades, the contribution of the immune system to tumor development has gained growing interest, and inflammation is definitively considered a hallmark of cancer progression. Cancer immune-editing is a complex process by which components of the immune system can either protect the host against cancer development or promote tumor escape by sculpting tumor immunogenicity and modulating the antitumor immune response. Efforts have focused on investigating the impact that immune cells have in the different stages of cancer progression, from the early onset of neoplastic transformation and the establishment of a growing tumor to metastatic dissemination and therapeutic intervention. Accordingly, immunotherapy has today firmly been recognized as a novel pillar of cancer care. The administration of checkpoint inhibitors, cancer vaccines, and specific cytokines has been promisingly used to stimulate the immune system to effectively recognize and eliminate cancer cells.

Although a number of studies have deeply investigated the interaction between cancer and the immune system, several aspects still need to be addressed.

The aim of this Special Issue is to provide an overview of recent advances in the field of “Immune Response to Cancer”. We therefore invite researchers to submit original papers and reviews to shed further light on the complex interaction between the immune system and neoplastic progression.

Dr. Diletta Di Mitri
Dr. Marco Erreni
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 short 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

tumor immunology
tumor microenvironment
cancer immuno-editing
cancer-related inflammation
immunotherapy
cancer imaging

Published Papers (6 papers)

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Research

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21 pages, 35569 KiB

Open AccessArticle

Multiplexed Imaging Mass Cytometry Analysis in Preclinical Models of Pancreatic Cancer

by Marco Erreni, Maria Rita Fumagalli, Damiano Zanini, Ermes Candiello, Giorgia Tiberi, Raffaella Parente, Raffaella D’Anna, Elena Magrini, Federica Marchesi, Paola Cappello and Andrea Doni

Int. J. Mol. Sci. 2024, 25(3), 1389; https://doi.org/10.3390/ijms25031389 - 23 Jan 2024

Viewed by 1238

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. PDAC is characterized by a complex tumor microenvironment (TME), that plays a pivotal role in disease progression and resistance to therapy. Investigating the spatial distribution and interaction of TME cells with the tumor is the basis for understanding the mechanisms underlying disease progression and represents a current challenge in PDAC research. Imaging mass cytometry (IMC) is the major multiplex imaging technology for the spatial analysis of tumor heterogeneity. However, there is a dearth of reports of multiplexed IMC panels for different preclinical mouse models, including pancreatic cancer. We addressed this gap by utilizing two preclinical models of PDAC: the genetically engineered, bearing KRAS–TP53 mutations in pancreatic cells, and the orthotopic, and developed a 28–marker panel for single–cell IMC analysis to assess the abundance, distribution and phenotypes of cells involved in PDAC progression and their reciprocal functional interactions. Herein, we provide an unprecedented definition of the distribution of TME cells in PDAC and compare the diversity between transplanted and genetic disease models. The results obtained represent an important and customizable tool for unraveling the complexities of PDAC and deciphering the mechanisms behind therapy resistance. Full article

(This article belongs to the Special Issue Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0)

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Review

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19 pages, 2104 KiB

Open AccessReview

Emerging Immune Checkpoint Molecules on Cancer Cells: CD24 and CD200

by Sun Young Moon, Minjoo Han, Gyoungah Ryu, Seong-Ah Shin, Jun Hyuck Lee and Chang Sup Lee

Int. J. Mol. Sci. 2023, 24(20), 15072; https://doi.org/10.3390/ijms242015072 - 11 Oct 2023

Cited by 3 | Viewed by 1447

Abstract

Cancer immunotherapy strategies are based on the utilization of immune checkpoint inhibitors to instigate an antitumor immune response. The efficacy of immune checkpoint blockade, directed at adaptive immune checkpoints, has been demonstrated in select cancer types. However, only a limited subset of patients has exhibited definitive outcomes characterized by a sustained response after discontinuation of therapy. Recent investigations have highlighted the significance of immune checkpoint molecules that are overexpressed in cancer cells and inhibit myeloid lineage immune cells within a tumor microenvironment. These checkpoints are identified as potential targets for anticancer immune responses. Notably, the immune checkpoint molecules CD24 and CD200 have garnered attention owing to their involvement in tumor immune evasion. CD24 and CD200 are overexpressed across diverse cancer types and serve as signaling checkpoints by engaging their respective receptors, Siglec-10 and CD200 receptor, which are expressed on tumor-associated myeloid cells. In this review, we summarized and discussed the latest advancements and insights into CD24 and CD200 as emergent immune checkpoint moieties, further delving into their therapeutic potentials for cancer treatment. Full article

(This article belongs to the Special Issue Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0)

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21 pages, 1231 KiB

Open AccessReview

Neoadjuvant Immunotherapy: A Promising New Standard of Care

by Emma Boydell, Jose L. Sandoval, Olivier Michielin, Michel Obeid, Alfredo Addeo and Alex Friedlaender

Int. J. Mol. Sci. 2023, 24(14), 11849; https://doi.org/10.3390/ijms241411849 - 24 Jul 2023

Cited by 6 | Viewed by 2485

Abstract

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various malignancies, with preclinical studies showing improved immune responses in the preoperative setting. FDA-approved neoadjuvant-immunotherapy-based approaches include triple-negative breast cancer and early non-small cell lung cancer on the basis of improvement in pathological response and event free survival. Nevertheless, current trials have only shown benefits in a fraction of patients. It is therefore crucial to identify predictive biomarkers to improve patient selection for such approaches. This review aims to provide an overview of potential biomarkers of neoadjuvant immunotherapy in early triple-negative breast cancer, bladder cancer, melanoma, non-small cell lung cancer, colorectal cancer and gastric cancer. By the extrapolation of the metastatic setting, we explore known predictive biomarkers, i.e., PD-L1, mismatch repair deficiency and tumour mutational burden, as well as potential early-disease-specific biomarkers. We also discuss the challenges of identifying reliable biomarkers and the need for standardized protocols and guidelines for their validation and clinical implementation. Full article

(This article belongs to the Special Issue Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0)

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22 pages, 1220 KiB

Open AccessReview

NK Cells in Cancer: Mechanisms of Dysfunction and Therapeutic Potential

by Federica Portale and Diletta Di Mitri

Int. J. Mol. Sci. 2023, 24(11), 9521; https://doi.org/10.3390/ijms24119521 - 30 May 2023

Cited by 5 | Viewed by 2613

Abstract

Natural killer cells (NK) are innate lymphocytes endowed with the ability to recognize and kill cancer cells. Consequently, adoptive transfer of autologous or allogeneic NK cells represents a novel opportunity in cancer treatment that is currently under clinical investigation. However, cancer renders NK cells dysfunctional, thus restraining the efficacy of cell therapies. Importantly, extensive effort has been employed to investigate the mechanisms that restrain NK cell anti-tumor function, and the results have offered forthcoming solutions to improve the efficiency of NK cell-based therapies. The present review will introduce the origin and features of NK cells, summarize the mechanisms of action and causes of dysfunction of NK cells in cancer, and frame NK cells in the tumoral microenvironment and in the context of immunotherapies. Finally, we will discuss therapeutic potential and current limitations of NK cell adoptive transfer in tumors. Full article

(This article belongs to the Special Issue Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0)

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28 pages, 2009 KiB

Open AccessReview

Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells

by María Luisa Sánchez-León, Carlos Jiménez-Cortegana, Silvia Silva Romeiro, Carmen Garnacho, Luis de la Cruz-Merino, Daniel J. García-Domínguez, Lourdes Hontecillas-Prieto and Víctor Sánchez-Margalet

Int. J. Mol. Sci. 2023, 24(6), 5208; https://doi.org/10.3390/ijms24065208 - 08 Mar 2023

Cited by 5 | Viewed by 2044

Abstract

Breast cancer (BC) continues to be the most diagnosed tumor in women and a very heterogeneous disease both inter- and intratumoral, mainly given by the variety of molecular profiles with different biological and clinical characteristics. Despite the advancements in early detection and therapeutic strategies, the survival rate is low in patients who develop metastatic disease. Therefore, it is mandatory to explore new approaches to achieve better responses. In this regard, immunotherapy arose as a promising alternative to conventional treatments due to its ability to modulate the immune system, which may play a dual role in this disease since the relationship between the immune system and BC cells depends on several factors: the tumor histology and size, as well as the involvement of lymph nodes, immune cells, and molecules that are part of the tumor microenvironment. Particularly, myeloid-derived suppressor cell (MDSC) expansion is one of the major immunosuppressive mechanisms used by breast tumors since it has been associated with worse clinical stage, metastatic burden, and poor efficacy of immunotherapies. This review focuses on the new immunotherapies in BC in the last five years. Additionally, the role of MDSC as a therapeutic target in breast cancer will be described. Full article

(This article belongs to the Special Issue Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0)

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23 pages, 1245 KiB

Open AccessReview

by Lorenzo Ruggieri, Anna Moretti, Rossana Berardi, Maria Silvia Cona, Davide Dalu, Cecilia Villa, Davide Chizzoniti, Sheila Piva, Anna Gambaro and Nicla La Verde

Int. J. Mol. Sci. 2023, 24(5), 4974; https://doi.org/10.3390/ijms24054974 - 04 Mar 2023

Cited by 3 | Viewed by 2186

Abstract

A significant proportion of patients treated for early breast cancer develop medium-term and late distant recurrence. The delayed manifestation of metastatic disease is defined as “dormancy”. This model describes the aspects of the clinical latency of isolated metastatic cancer cells. Dormancy is regulated by extremely complex interactions between disseminated cancer cells and the microenvironment where they reside, the latter in turn influenced directly by the host. Among these entangled mechanisms, inflammation and immunity may play leading roles. This review is divided into two parts: the first describes the biological underpinnings of cancer dormancy and the role of the immune response, in particular, for breast cancer; the second provides an overview of the host-related factors that may influence systemic inflammation and immune response, subsequently impacting the dynamics of breast cancer dormancy. The aim of this review is to provide physicians and medical oncologists a useful tool to understand the clinical implications of this relevant topic. Full article

(This article belongs to the Special Issue Immune Response to Cancer: From Tumor Onset to Therapeutic Approach 2.0)

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