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Cancers
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Immune Microenvironment and Cancer Progression
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Immune Microenvironment and Cancer Progression

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 29638

Special Issue Editor

Dr. Esteban Orenes-Piñero

E-Mail Website
Guest Editor
1. Department of Biochemistry and Molecular Biology-A, Universidad de Murcia, 30071 Murcia, Spain
2. Proteomic Unit IMIB-Arrixaca, 30071 Murcia, Spain
Interests: proteomics; genomics; cancer; nutrition; elderly; COVID-19; biochemistry; molecular biology

Special Issue Information

Dear Colleagues,

Conventional clinical and pathological risk prediction in cancer patients is usually achieved by histopathological evaluation of tissue samples obtained during surgical removal of the primary tumor. In addition, histological or radiological analyses of tumor draining and regional lymph nodes, as well as of distant organs, are performed to identify evidence of metastases. The tumor staging classification (TNM) summarizes data on the extent of tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N), and evidence of metastases (M). Importantly, in daily practice and in guidelines, the TNM category is linked directly to treatment strategies, and as such, changes in the TNM staging system have a considerable and direct impact on the cancer care that patients receive.

This way, the predictive accuracy of the TNM traditional staging system assumes that disease progression is a tumor cell autonomous process, and it does not take into consideration the effects of the host immune response. However, the interplay between cancer and immune cells is a major determinant in cancer progression, and tumor-infiltrating lymphocytes (TILs) are emerging as a powerful prognostic marker and therapeutic target in oncology.

Moreover, the tumor microenvironment is shaped by interactions between malignant cells and host immune cells that represent an integral component of solid tumors. The development of an efficient antitumor immune response decreases the probability of tumor recurrence and metastasis formation, thus positively influencing the outcome of the disease. Importantly, the presence of high numbers of T-lymphocytes has been reported to be an indicator of good prognosis in cancers such as colon cancer, melanoma, lung carcinoma, pancreatic cancer, hepatocellular carcinoma, breast cancer, and even brain metastases. In this scenario, the quantification of in situ immune cell infiltrates in tumor samples has been shown to be a better predictor of patient overall survival and disease-free-survival than the TNM classification system in several studies.

With the development of immunohistochemistry, more subtypes of TILs have been discovered. CD3+, a biomarker of T-lymphocytes, is expressed in almost all T-lymphocytes. In addition, T lymphocyte cell surface markers include mainly the following subtypes: CD8+ cytotoxic T-lymphocytes (CTL), CD4+ T helper lymphocytes (Th), CD45RO+ memory T cells, and FOXP3+ regulatory cells (Tregs), among others. The role of these TILs in different cancer types will be discussed in this Special Issue.

Dr. Esteban Orenes-Piñero
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.

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Published Papers (6 papers)

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Research

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15 pages, 3509 KiB  
Article
Intratumoral Niches of B Cells and Follicular Helper T Cells, and the Absence of Regulatory T Cells, Associate with Longer Survival in Early-Stage Oral Tongue Cancer Patients
by Chumut Phanthunane, Rebecca Wijers, Maria J. De Herdt, Senada Koljenović, Stefan Sleijfer, Robert J. Baatenburg de Jong, José Angelito U. Hardillo, Reno Debets and Hayri E. Balcioglu
Cancers 2022, 14(17), 4298; https://doi.org/10.3390/cancers14174298 - 1 Sep 2022
Cited by 8 | Viewed by 2664
Abstract
In early oral squamous cell carcinoma (OSCC), the occurrence of clusters between CD20 B cells and CD4 T cells in the invasive margin (IM) can be captured by using the CD20 cluster score, and is positively associated with patient survival. However, the exact [...] Read more.
In early oral squamous cell carcinoma (OSCC), the occurrence of clusters between CD20 B cells and CD4 T cells in the invasive margin (IM) can be captured by using the CD20 cluster score, and is positively associated with patient survival. However, the exact contribution of different CD4 T cell subsets, as well as B cell subsets toward patient prognosis is largely unknown. To this end, we studied regulatory T cells ((Treg cells) FOXP3 and CD4), T helper-type 1 cells ((Th1 cells) Tbet and CD4), follicular helper T cells ((Tfh cells) Bcl6 and CD4), B cells (CD20), germinal center B cells ((GC B cells) BCL6 and CD20), and follicular dendritic cells ((fDCs) CD21) for their density, location, and interspacing using multiplex in situ immunofluorescence of 75 treatment-naïve, primary OSCC patients. We observed that Treg, Th1-, Tfh-, and GC B cells, but not fDCs, were abundantly present in the stroma as compared with the tumor, and in the IM as compared with in the center of the tumor. Patients with high CD20 cluster scores had a high density of all three CD4 T cell subsets and GC B cells in the stromal IM as compared with patients with low CD20 cluster scores. Notably, enriched abundance of Tfh cells (HR 0.20, p = 0.04), and diminished abundance of Treg cells (HR 0.10, p = 0.03), together with an overall short distance between Tfh and B cells (HR:0.08, p < 0.01), but not between Treg and B cells (HR 0.43, p = 0.28), were significantly associated with overall survival of patients with OSCC. Our study identified the prognostic value of clusters between CD20 B cells and Tfh cells in the stromal IM of OSCC patients, and enabled an improved understanding of the clinical value of a high CD20 cluster score, which requires validation in larger clinical cohorts. Full article
(This article belongs to the Special Issue Immune Microenvironment and Cancer Progression)
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Review

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26 pages, 1535 KiB  
Review
A Journey through the Inter-Cellular Interactions in the Bone Marrow in Multiple Myeloma: Implications for the Next Generation of Treatments
by Rosario Hervás-Salcedo and Beatriz Martín-Antonio
Cancers 2022, 14(15), 3796; https://doi.org/10.3390/cancers14153796 - 4 Aug 2022
Cited by 7 | Viewed by 3021
Abstract
Tumors are composed of a plethora of extracellular matrix, tumor and non-tumor cells that form a tumor microenvironment (TME) that nurtures the tumor cells and creates a favorable environment where tumor cells grow and proliferate. In multiple myeloma (MM), the TME is the [...] Read more.
Tumors are composed of a plethora of extracellular matrix, tumor and non-tumor cells that form a tumor microenvironment (TME) that nurtures the tumor cells and creates a favorable environment where tumor cells grow and proliferate. In multiple myeloma (MM), the TME is the bone marrow (BM). Non-tumor cells can belong either to the non-hematological compartment that secretes soluble mediators to create a favorable environment for MM cells to grow, or to the immune cell compartment that perform an anti-MM activity in healthy conditions. Indeed, marrow-infiltrating lymphocytes (MILs) are associated with a good prognosis in MM patients and have served as the basis for developing different immunotherapy strategies. However, MM cells and other cells in the BM can polarize their phenotype and activity, creating an immunosuppressive environment where immune cells do not perform their cytotoxic activity properly, promoting tumor progression. Understanding cell–cell interactions in the BM and their impact on MM proliferation and the performance of tumor surveillance will help in designing efficient anti-MM therapies. Here, we take a journey through the BM, describing the interactions of MM cells with cells of the non-hematological and hematological compartment to highlight their impact on MM progression and the development of novel MM treatments. Full article
(This article belongs to the Special Issue Immune Microenvironment and Cancer Progression)
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22 pages, 1118 KiB  
Review
Estrogens, Cancer and Immunity
by Izabela Orzołek, Jan Sobieraj and Joanna Domagała-Kulawik
Cancers 2022, 14(9), 2265; https://doi.org/10.3390/cancers14092265 - 30 Apr 2022
Cited by 29 | Viewed by 3794
Abstract
Sex hormones are included in many physiological and pathological pathways. Estrogens belong to steroid hormones active in female sex. Estradiol (E2) is the strongest female sex hormone and, with its receptors, contributes to oncogenesis, cancer progression and response to treatment. In recent years, [...] Read more.
Sex hormones are included in many physiological and pathological pathways. Estrogens belong to steroid hormones active in female sex. Estradiol (E2) is the strongest female sex hormone and, with its receptors, contributes to oncogenesis, cancer progression and response to treatment. In recent years, a role of immunosurveillance and suppression of immune response in malignancy has been well defined, forming the basis for cancer immunotherapy. The interplay of sex hormones with cancer immunity, as well as the response to immune checkpoint inhibitors, is of interest. In this review, we investigate the impact of sex hormones on natural immune response with respect to main active elements in anticancer immune surveillance: dendritic cells, macrophages, lymphocytes and checkpoint molecules. We describe the main sex-dependent tumors and the contribution of estrogen in their progression, response to treatment and especially modulation of anticancer immune response. Full article
(This article belongs to the Special Issue Immune Microenvironment and Cancer Progression)
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55 pages, 6375 KiB  
Review
Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers
by Alicia Cristina Peña-Romero and Esteban Orenes-Piñero
Cancers 2022, 14(7), 1681; https://doi.org/10.3390/cancers14071681 - 25 Mar 2022
Cited by 134 | Viewed by 12160
Abstract
Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the [...] Read more.
Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the existence of a tumour also cause our immune system (IS) to be put on alert. Indeed, the link between immunology and cancer is evident these days, with IS being used as one of the important targets for treating cancer. Our IS is able to eliminate those abnormal or damaged cells found in our body, preventing the uncontrolled proliferation of tumour cells that can lead to cancer. However, in several cases, tumour cells can escape from the IS. It has been observed that immune cells, the extracellular matrix, blood vessels, fat cells and various molecules could support tumour growth and development. Thus, the developing tumour receives structural support, irrigation and energy, among other resources, making its survival and progression possible. All these components that accompany and help the tumour to survive and to grow are called the tumour microenvironment (TME). Given the importance of its presence in the tumour development process, this review will focus on one of the components of the TME: immune cells. Immune cells can support anti-tumour immune response protecting us against tumour cells; nevertheless, they can also behave as pro-tumoural cells, thus promoting tumour progression and survival. In this review, the anti-tumour and pro-tumour immunity of several immune cells will be discussed. In addition, the TME influence on this dual effect will be also analysed. Full article
(This article belongs to the Special Issue Immune Microenvironment and Cancer Progression)
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14 pages, 1839 KiB  
Review
Meningioma–Brain Crosstalk: A Scoping Review
by Josefine de Stricker Borch, Jeppe Haslund-Vinding, Frederik Vilhardt, Andrea Daniela Maier and Tiit Mathiesen
Cancers 2021, 13(17), 4267; https://doi.org/10.3390/cancers13174267 - 24 Aug 2021
Cited by 15 | Viewed by 3743
Abstract
Background: In recent years, it has become evident that the tumoral microenvironment (TME) plays a key role in the pathogenesis of various cancers. In meningiomas, however, the TME is poorly understood, and it is unknown if glia cells contribute to meningioma growth [...] Read more.
Background: In recent years, it has become evident that the tumoral microenvironment (TME) plays a key role in the pathogenesis of various cancers. In meningiomas, however, the TME is poorly understood, and it is unknown if glia cells contribute to meningioma growth and behaviour. Objective: This scoping review investigates if the literature describes and substantiates tumour–brain crosstalk in meningiomas and summarises the current evidence regarding the role of the brain parenchyma in the pathogenesis of meningiomas. Methods: We identified studies through the electronic database PubMed. Articles describing glia cells and cytokines/chemokines in meningiomas were selected and reviewed. Results: Monocytes were detected as the most abundant infiltrating immune cells in meningiomas. Only brain-invasive meningiomas elicited a monocytic response at the tumour–brain interface. The expression of cytokines/chemokines in meningiomas has been studied to some extent, and some of them form autocrine loops in the tumour cells. Paracrine interactions between tumour cells and glia cells have not been explored. Conclusion: It is unknown to what extent meningiomas elicit an immune response in the brain parenchyma. We speculate that tumour–brain crosstalk might only be relevant in cases of invasive meningiomas that disrupt the pial–glial basement membrane. Full article
(This article belongs to the Special Issue Immune Microenvironment and Cancer Progression)
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Other

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15 pages, 1581 KiB  
Systematic Review
Tumor-Infiltrating Lymphocytes as Biomarkers of Treatment Response and Long-Term Survival in Patients with Rectal Cancer: A Systematic Review and Meta-Analysis
by Adile Orhan, Faisal Khesrawi, Michael Tvilling Madsen, Rasmus Peuliche Vogelsang, Niclas Dohrn, Anne-Marie Kanstrup Fiehn and Ismail Gögenur
Cancers 2022, 14(3), 636; https://doi.org/10.3390/cancers14030636 - 27 Jan 2022
Cited by 17 | Viewed by 3183
Abstract
Neoadjuvant chemoradiotherapy (NCRT) is indicated in locally advanced rectal cancer (LARC) to downstage tumors before surgery. Watchful waiting may be a treatment option to avoid surgery in patients, obtaining a complete clinical response. However, biomarkers predictive of treatment response and long-term prognosis are [...] Read more.
Neoadjuvant chemoradiotherapy (NCRT) is indicated in locally advanced rectal cancer (LARC) to downstage tumors before surgery. Watchful waiting may be a treatment option to avoid surgery in patients, obtaining a complete clinical response. However, biomarkers predictive of treatment response and long-term prognosis are lacking. Here we investigated tumor-infiltrating lymphocytes (TILs) in pretherapeutic biopsies as predictive and prognostic biomarkers. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. In total, 429 articles were identified, of which 19 studies were included in the systematic review and 14 studies in the meta-analysis. Patients with high pretherapeutic CD8+ TILs density had an increased likelihood of achieving a pathological complete response (RR = 2.71; 95% CI: 1.58–4.66) or a complete or near-complete pathological treatment response (RR = 1.86; 95% CI: 1.50–2.29). Furthermore, high CD8+ TILs density was a favorable prognostic factor for disease-free survival (HR = 0.57; 95% CI: 0.38–0.86) and overall survival (HR = 0.43; 95% CI: 0.27–0.69). CD3+, CD4+, and FOXP3+ TILs were not identified as predictive or prognostic biomarkers. Thus, assessing pretherapeutic CD8+ TILs density may assist in identifying patients with increased sensitivity to NCRT and favorable long-term prognosis. Full article
(This article belongs to the Special Issue Immune Microenvironment and Cancer Progression)
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