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Cancers
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Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to...
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Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 5 December 2024 | Viewed by 2849

Special Issue Editors

Prof. Dr. Ira-Ida Skvortsova

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Guest Editor
Department of Therapeutic Radiology and Oncology, Tyrolean Cancer Research Institute, Medical University of Innsbruck, Anichstr. 35, A-6020 Innsbruck, Austria
Interests: cancer metastasis; cancer stem cells; therapy resistance; molecular mechanisms; cancer microenvironment
Special Issues, Collections and Topics in MDPI journals
Dr. Johjong Huang

E-Mail Website
Guest Editor
1. Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2. Department of Medical Humanities and Education, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: cancer comorbidity; cancer treatment complication; cancer prognosis; public health
Special Issues, Collections and Topics in MDPI journals
Dr. Hsin-Hua Lee

E-Mail Website
Guest Editor
Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Interests: radiotherapy and combination therapy in cancer; image guidance; biomarker; palliative care; IMRT; VMAT; IGRT; tomotherapy; SMART
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The interactions between cells in the ecosystem where a tumor resides contribute to cancer cell progression, invasion, and metastasis. In 1889, Dr. Stephen Paget proposed the “seed and soil” hypothesis, highlighting the importance of a fertile environment for the tumor cells to grow. Tumor-infiltrating cells, mainly immune cells, produce inflammatory mediators to form a microenvironment promoting cancer development and progression. Mounting evidence from preclinical studies and clinical trials have shown that the combination of immune-checkpoint blockade and radiation therapy (RT) result in a synergy.

With the advent of immunotherapy and innovative imaging technology, more abscopal effects upon RT in combination with immune-checkpoint inhibition have been reported. An abscopal effect is an appealing phenomenon after RT activates the antitumor immune response, and was described as early as 1953. From a molecular standpoint, RT causes not only direct DNA damage but also ample reactive-oxygen-species-dependent damage to DNA, potentially culminating in the permanent inactivation of cell division, cellular senescence, or the initiation of cell death programs. While many recent studies clearly attribute the abscopal effect to the activation of the immune system against cancer cells, the cellular and molecular mechanisms remain mysterious.

We welcome in-depth reviews and original articles from the latest research on multi-modality treatment strategies (chemotherapy, immunotherapy, and targeted therapy combined with RT) addressing the roles and interactions of the abscopal effect, micro-environmental factors, radiosensitizers, ground-breaking RT technology, and natural food extracts to overcome treatment complications, as well as biomarkers for predicting RT outcome.

You may choose our Joint Special Issue in Cells.

Prof. Dr. Ira-Ida Skvortsova
Dr. Johjong Huang
Dr. Hsin-Hua Lee
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. 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

  • tumor microenvironment
  • natural food extracts
  • molecular markers
  • abscopal effect
  • RT technology
  • prognosis
  • side effects and abscopal effects

Published Papers (4 papers)

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Research

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12 pages, 1549 KiB  
Article
A Head-to-Head Comparison of the First-Line Treatments for Locally Advanced or Metastatic Urothelial Cancer: Is There Still a Role for Chemotherapy?
by Lorenzo Gasperoni, Luna Del Bono, Andrea Ossato, Emilio Francesco Giunta, Andrea Messori and Vera Damuzzo
Cancers 2024, 16(13), 2400; https://doi.org/10.3390/cancers16132400 - 29 Jun 2024
Viewed by 361
Abstract
Background: Patients with locally advanced/metastatic urothelial cancer have been conventionally treated with platinum-based chemotherapy. Recently, numerous new treatments have been proposed to improve overall survival (OS) and reduce adverse effects, but no direct head-to-head comparisons among these agents are available. Methods: The treatments [...] Read more.
Background: Patients with locally advanced/metastatic urothelial cancer have been conventionally treated with platinum-based chemotherapy. Recently, numerous new treatments have been proposed to improve overall survival (OS) and reduce adverse effects, but no direct head-to-head comparisons among these agents are available. Methods: The treatments evaluated in our analyses included (a) monotherapy with immune checkpoint inhibitors (ICI); (b) combinations of an ICI with chemotherapy; and (c) combinations of an ICI with other drugs. Using OS as the endpoint, a series of indirect comparisons were performed to rank the most effective regimens against both chemotherapy and each other. Our analysis was based on the application of an artificial intelligence software program (IPDfromKM method) that reconstructs individual patient data from the information reported in the graphs of Kaplan–Meier curves. Results: A total of five studies published in six articles were included. In our main analysis, nivolumab plus chemotherapy showed better OS compared to chemotherapy (HR = 0.70, 95% CI: 0.59–0.82), while durvalumab plus tremelimumab showed no OS benefit (HR = 0.95, 95% CI 0.82–1.11). More interestingly, enfortumab vedotin plus pembrolizumab significantly prolonged OS compared to both chemotherapy alone (HR = 0.53, 95% CI 0.45–0.63) and nivolumab plus chemotherapy (HR = 0.76, 95% CI 0.60–0.97). Discussion and conclusion: Among new treatments for locally advanced and metastatic urothelial cancer, enfortumab vedotin plus pembrolizumab showed the best efficacy in terms of OS. Our results support the use of this combination as a first-line treatment in this setting. Full article
(This article belongs to the Special Issue Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology)
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30 pages, 12824 KiB  
Article
Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients
by Lavanya Lokhande, Daniel Nilsson, Joana de Matos Rodrigues, May Hassan, Lina M. Olsson, Paul-Theodor Pyl, Louella Vasquez, Anna Porwit, Anna Sandström Gerdtsson, Mats Jerkeman and Sara Ek
Cancers 2024, 16(13), 2289; https://doi.org/10.3390/cancers16132289 - 21 Jun 2024
Viewed by 470
Abstract
With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue [...] Read more.
With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57−) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL. Full article
(This article belongs to the Special Issue Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology)
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16 pages, 4086 KiB  
Article
The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study
by Ayaka Asakawa, Ryoto Yoshimoto, Maki Kobayashi, Nanae Izumi, Takanori Maejima, Tsuneo Deguchi, Kazuishi Kubota, Hisashi Takahashi, Miyuki Yamada, Sachiko Ishibashi, Iichiroh Onishi, Yuko Kinowaki, Morito Kurata, Masashi Kobayashi, Hironori Ishibashi, Kenichi Okubo, Kenichi Ohashi, Masanobu Kitagawa and Kouhei Yamamoto
Cancers 2024, 16(11), 2140; https://doi.org/10.3390/cancers16112140 - 4 Jun 2024
Viewed by 661
Abstract
Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and [...] Read more.
Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163+PD-L1+ macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68+, CD163+, and CK+ cells with PD-L1+ phenotypes had higher B7-H3 expression compared to PD-L1− cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies. Full article
(This article belongs to the Special Issue Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology)
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Review

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23 pages, 2105 KiB  
Review
Immune Regulation and Immune Therapy in Melanoma: Review with Emphasis on CD155 Signalling
by Li-Ying Wu, Su-Ho Park, Haakan Jakobsson, Mark Shackleton and Andreas Möller
Cancers 2024, 16(11), 1950; https://doi.org/10.3390/cancers16111950 - 21 May 2024
Viewed by 838
Abstract
Melanoma is commonly diagnosed in a younger population than most other solid malignancies and, in Australia and most of the world, is the leading cause of skin-cancer-related death. Melanoma is a cancer type with high immunogenicity; thus, immunotherapies are used as first-line treatment [...] Read more.
Melanoma is commonly diagnosed in a younger population than most other solid malignancies and, in Australia and most of the world, is the leading cause of skin-cancer-related death. Melanoma is a cancer type with high immunogenicity; thus, immunotherapies are used as first-line treatment for advanced melanoma patients. Although immunotherapies are working well, not all the patients are benefitting from them. A lack of a comprehensive understanding of immune regulation in the melanoma tumour microenvironment is a major challenge of patient stratification. Overexpression of CD155 has been reported as a key factor in melanoma immune regulation for the development of therapy resistance. A more thorough understanding of the actions of current immunotherapy strategies, their effects on immune cell subsets, and the roles that CD155 plays are essential for a rational design of novel targets of anti-cancer immunotherapies. In this review, we comprehensively discuss current anti-melanoma immunotherapy strategies and the immune response contribution of different cell lineages, including tumour endothelial cells, myeloid-derived suppressor cells, cytotoxic T cells, cancer-associated fibroblast, and nature killer cells. Finally, we explore the impact of CD155 and its receptors DNAM-1, TIGIT, and CD96 on immune cells, especially in the context of the melanoma tumour microenvironment and anti-cancer immunotherapies. Full article
(This article belongs to the Special Issue Latest Breakthroughs in Tumor Immune Microenvironment: From Cellular Discovery to Cutting-Edge Technology)
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