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Role of Innate Immune Cells in the Tumor Progression and Metastasis

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 26953

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Special Issue Editor

Dr. Lorenzo Mortara

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Guest Editor

Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy
Interests: human tumor angiogenesis; innate immune cells in the tumor microenvironment; natural killer cells and macrophages in human cancers; evaluating novel immunotherapeutic interventions based on immunocitokynes TNF and IL-2, in combination setting against tumor development and metastasis in preclinical tumor murine models.
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Special Issue Information

Dear Colleagues,

The milieu in which the tumor grows and proliferates is characterized by the tumor microenvironment, harboring both malignant and non-malignant cells. Among non-malignant cells, consisting of host-derived stromal, immune, and endothelial cells, innate immune cells can play dual and paradoxical roles in tumor development and dissemination. Indeed, they have the potential to recognize and destroy tumor cells, and, on the other hand, they can become pro-tumorigenic by helping the development of the tumor mass, as well as progression, invasiveness, dissemination, and clinical outcome. For cell growth, progression and dissemination, tumor cells must interact with innate immune cells in order to regulate a complex modified tissue compartment. In the tumor microenvironment, there are different key processes that must be established to ensure tumor growth, such as triggering a tumor promoting inflammation, inducing an antigenic immune evasion, activating an angiogenesis switch, and driving metastatic competence. All these factors highlight the key role of the immune system in neoplastic disease.

The aim of this Special Issue is to provide a broad overview on the topic of “Role of Innate Immune Cells in the Tumor Progression and Metastasis” in the context of human cancers, preclinical cancer models, drug resistance, and therapy. To this end, we welcome experts in this field to contribute with original research, mini and full reviews, and perspectives. Contributions are not limited to the fields that are mentioned in the keywords.

Dr. Lorenzo Mortara
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

cancer
innate immune cells
tumor microenvironment
inflammation
angiogenesis
metastasis
cell polarization
cytokines
chemokines
tumor drug resistance

Published Papers (5 papers)

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Research

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19 pages, 2417 KiB

Open AccessArticle

An In Vitro Model of Mast Cell Recruitment and Activation by Breast Cancer Cells Supports Anti-Tumoral Responses

by Angélica Aponte-López, Jennifer Enciso, Samira Muñoz-Cruz and Ezequiel M. Fuentes-Pananá

Int. J. Mol. Sci. 2020, 21(15), 5293; https://doi.org/10.3390/ijms21155293 - 26 Jul 2020

Cited by 5 | Viewed by 2968

Abstract

Breast cancer (BrC) affects millions of women yearly. Mast cells (MCs) are common components of breast tumors with documented agonistic and antagonistic roles in tumor progression. Understanding the participation of MCs in BrC may lead to new therapies to control tumor growth. In this study, we looked into mechanistic models of MC responses triggered by BrC cells (BrCC), assessing both early degranulation and late transcriptional activities. We used aggressive and non-aggressive BrCC to model the progressive staging of the disease over HMC1 and LAD-2 human MC lines. We found that both MC lines were chemoattracted by all BrCC, but their activation was preferentially induced by aggressive lines, finding differences in their active transcriptional programs, both at basal level and after stimulation. Among those genes with altered expression were down-regulated SPP1, PDCD1, IL17A and TGFB1 and up-regulated KITLG and IFNG. A low expression of SPP1 and a high expression of KITLG and IFNG were associated with increased overall survival of BrC patients from public databases. The set of altered genes is more often associated with tumor stromas enriched with anti-tumoral signals, suggesting that MCs may participate in tumor control. Full article

(This article belongs to the Special Issue Role of Innate Immune Cells in the Tumor Progression and Metastasis)

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Review

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22 pages, 840 KiB

Open AccessReview

Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

by Pierpaolo Ginefra, Girieca Lorusso and Nicola Vannini

Int. J. Mol. Sci. 2020, 21(12), 4441; https://doi.org/10.3390/ijms21124441 - 22 Jun 2020

Cited by 19 | Viewed by 4617

Abstract

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients. Full article

(This article belongs to the Special Issue Role of Innate Immune Cells in the Tumor Progression and Metastasis)

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24 pages, 3300 KiB

Open AccessReview

Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

by Annalisa Del Prete, Francesca Sozio, Ilaria Barbazza, Valentina Salvi, Laura Tiberio, Mattia Laffranchi, Angela Gismondi, Daniela Bosisio, Tiziana Schioppa and Silvano Sozzani

Int. J. Mol. Sci. 2020, 21(11), 3930; https://doi.org/10.3390/ijms21113930 - 30 May 2020

Cited by 37 | Viewed by 4570

Abstract

Dendritic cells (DCs) constitute a complex network of cell subsets with common functions but also with many divergent aspects. All dendritic cell subsets share the ability to prime T cell response and to undergo a complex trafficking program related to their stage of maturation and function. For these reasons, dendritic cells are implicated in a large variety of both protective and detrimental immune responses, including a crucial role in promoting anti-tumor responses. Although cDC1s are the most potent subset in tumor antigen cross-presentation, they are not sufficient to induce full-strength anti-tumor cytotoxic T cell response and need close interaction and cooperativity with the other dendritic cell subsets, namely cDC2s and pDCs. This review will take into consideration different aspects of DC biology, including the functional role of dendritic cell subsets in both fostering and suppressing tumor growth, the mechanisms underlying their recruitment into the tumor microenvironment, as well as the prognostic value and the potentiality of dendritic cell therapeutic targeting. Understanding the specificity of dendritic cell subsets will allow to gain insights on role of these cells in pathological conditions and to design new selective promising therapeutic approaches. Full article

(This article belongs to the Special Issue Role of Innate Immune Cells in the Tumor Progression and Metastasis)

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22 pages, 1209 KiB

Open AccessReview

Influence of Innate Immunity on Cancer Cell Stemness

by Anna Pastò, Francesca Maria Consonni and Antonio Sica

Int. J. Mol. Sci. 2020, 21(9), 3352; https://doi.org/10.3390/ijms21093352 - 09 May 2020

Cited by 19 | Viewed by 4639

Abstract

Even if cancer stem cells (CSCs) represent only a small proportion of the tumor mass, they significantly account for tumor maintenance, resistance to therapies, relapse and metastatic spread, due to their increased capacity of self-renewal, multipotency, tumorigenicity and quiescence. Emerging evidence suggests that the immune contexture within the tumor microenvironment (TME) determines both the response to therapy and the clinical outcome. In this context, CSCs acquire immune evasion skills by editing immune cell functions and sculpting the immunosuppressive landscape of TME. Reciprocally, infiltrating immune cells influence CSCs self-renewal, tumorigenicity and metastasis. In this review, we summarize the immunomodulatory properties of CSCs, as well as the impact of innate immune cells on cancer cells stemness in the different phases of cancer immunoediting process and neoplastic progression. Full article

(This article belongs to the Special Issue Role of Innate Immune Cells in the Tumor Progression and Metastasis)

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24 pages, 2146 KiB

Open AccessReview

The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors

by Denisa Baci, Annalisa Bosi, Matteo Gallazzi, Manuela Rizzi, Douglas M. Noonan, Alessandro Poggi, Antonino Bruno and Lorenzo Mortara

Int. J. Mol. Sci. 2020, 21(9), 3125; https://doi.org/10.3390/ijms21093125 - 28 Apr 2020

Cited by 77 | Viewed by 9627

Abstract

Ovarian cancer (OvCA) accounts for one of the leading causes of death from gynecologic malignancy. Despite progress in therapy improvements in OvCA, most patients develop a recurrence after first-line treatments, dependent on the tumor and non-tumor complexity/heterogeneity of the neoplasm and its surrounding tumor microenvironment (TME). The TME has gained greater attention in the design of specific therapies within the new era of immunotherapy. It is now clear that the immune contexture in OvCA, here referred as tumor immune microenvironment (TIME), acts as a crucial orchestrator of OvCA progression, thus representing a necessary target for combined therapies. Currently, several advancements of antitumor immune responses in OvCA are based on the characterization of tumor-infiltrating lymphocytes, which have been shown to correlate with a significantly improved clinical outcome. Here, we reviewed the literature on selected TIME components of OvCA, such as macrophages, neutrophils, γδ T lymphocytes, and natural killer (NK) cells; these cells can have a role in either supporting or limiting OvCA, depending on the TIME stimuli. We also reviewed and discussed the major (immune)-therapeutic approaches currently employed to target and/or potentiate macrophages, neutrophils, γδ T lymphocytes, and NK cells in the OvCA context. Full article

(This article belongs to the Special Issue Role of Innate Immune Cells in the Tumor Progression and Metastasis)

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