Topic Editors

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China

Inflammatory Tumor Immune Microenvironment

Abstract submission deadline
15 January 2025
Manuscript submission deadline
15 March 2025
Viewed by
16659

Topic Information

Dear Colleagues,

Cancer cells, as well as surrounding stromal and inflammatory cells, engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment. The inflammatory tumor microenvironment plays multiple roles in different stages of tumor development, including tumorigenesis, primary tumor growth and distant metastasis. Cells within the tumor microenvironment are highly plastic, continuously changing their phenotypic and functional characteristics. High-throughput single-cell methods, including single-cell sequencing and mass spectrometry, have greatly improved the understanding of inflammatory tumor microenvironment in the past few years. Metabolic adaptation, epigenetic heterogeneity and post-translational modification continue to propel the conceptual advances of inflammatory tumor microenvironment. Given the critical involvement of the inflammatory tumor microenvironment in tumor development, investigations into the inflammatory tumor microenvironment may favor further development of anti-cancer therapies.

This Research Topic aims to shed light on inflammatory tumor microenvironment in tumorigenesis, primary tumor growth and distant metastasis. We welcome contributions in form of Original Research articles, Reviews and Mini-Reviews that cover but are not limited to the following topics related to inflammatory tumor microenvironment in cancer:

  1. Inflammation-manipulated immune cell plasticity within the tumor microenvironment.
  2. Inflammation-involved immune exhaustion in cancer.
  3. Mechanisms of inflammatory leukocytes accumulation in tumor microenvironment. 
  4. Metabolic adaptation of inflammatory cells in tumor microenvironment.
  5. Targeting pro-tumoral inflammation in tumor therapy.
  6. Signaling pathways of inflammation-induced tumorigenesis.
  7. Plasticity of the pre-metastatic microenvironment.
  8. Functions and mechanisms of action of inflammatory cytokines in the tumor microenvironment.
  9. Epigenetic modifications in the tumor microenvironment.
  10. Immune checkpoints in tumor microenvironment.
  11. Development of tumor-related markers (diagnostic, surveillance, prognostic and immune checkpoints).

Dr. William Cho
Dr. Anquan Shang
Topic Editors

Keywords

  • tumor microenvironment
  • immune microenvironment
  • inflammation
  • neutrophil
  • macrophage

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
BioMedInformatics
biomedinformatics
- - 2021 21 Days CHF 1000 Submit
Cancers
cancers
5.2 7.4 2009 17.9 Days CHF 2900 Submit
Cells
cells
6.0 9.0 2012 16.6 Days CHF 2700 Submit
Diagnostics
diagnostics
3.6 3.6 2011 20.7 Days CHF 2600 Submit
Immuno
immuno
- - 2021 20.7 Days CHF 1000 Submit
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900 Submit

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Published Papers (8 papers)

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22 pages, 11501 KiB  
Article
Radiation-Induced Innate Neutrophil Response in Tumor Is Mediated by the CXCLs/CXCR2 Axis
by Faya Zhang, Oscar Mulvaney, Erica Salcedo, Subrata Manna, James Z. Zhu, Tao Wang, Chul Ahn, Laurentiu M. Pop and Raquibul Hannan
Cancers 2023, 15(23), 5686; https://doi.org/10.3390/cancers15235686 - 01 Dec 2023
Viewed by 1202
Abstract
The early events that lead to the inflammatory and immune-modulatory effects of radiation therapy (RT) in the tumor microenvironment (TME) after its DNA damage response activating the innate DNA-sensing pathways are largely unknown. Neutrophilic infiltration into the TME in response to RT is [...] Read more.
The early events that lead to the inflammatory and immune-modulatory effects of radiation therapy (RT) in the tumor microenvironment (TME) after its DNA damage response activating the innate DNA-sensing pathways are largely unknown. Neutrophilic infiltration into the TME in response to RT is an early innate inflammatory response that occurs within 24–48 h. Using two different syngeneic murine tumor models (RM-9 and MC-38), we demonstrated that CXCR2 blockade significantly reduced RT-induced neutrophilic infiltration. CXCR2 blockade showed the same effects on RT-induced tumor inhibition and host survival as direct neutrophil depletion. Neutrophils highly and preferentially expressed CXCR2 compared to other immune cells. Importantly, RT induced both gene and protein expression of CXCLs in the TME within 24 h, attracting neutrophils into the tumor. Expectedly, RT also upregulated the gene expression of both cGAS and AIM2 DNA-sensing pathways in cGAS-positive MC-38 tumors but not in cGAS-negative RM-9 tumors. Activation of these pathways resulted in increased IL-1β, which is known to activate the CXCLs/CXCR2 axis. Gene ontology analysis of mRNA-Seq supported these findings. Taken together, the findings suggest that the CXCLs/CXCR2 axis mediates the RT-induced innate inflammatory response in the TME, likely translating the effects of innate DNA-sensing pathways that are activated in response to RT-induced DNA damage. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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16 pages, 2384 KiB  
Article
Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling
by Lei Wang, Weijun Yi, Li Ma, Emily Lecea, Lori A. Hazlehurst, Donald A. Adjeroh and Gangqing Hu
Cancers 2023, 15(21), 5148; https://doi.org/10.3390/cancers15215148 - 26 Oct 2023
Viewed by 1542
Abstract
Bone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated [...] Read more.
Bone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated in drug resistance. Through a sophisticated analysis of public expression data from unexpanded BM MSCs, we uncovered a positive association between iMSC signature expression and minimal residual disease. While in vitro expansion generally results in the loss of the iMSC signature, our meta-analysis of additional public expression data demonstrated that cytokine stimulation, including IL1-β and TNF-α, as well as immune cells such as neutrophils, macrophages, and MM cells, can reactivate the signature expression of iMSCs to varying extents. These findings underscore the importance and potential utility of cytokine stimulation in mimicking the gene expression signature of early passage of iMSCs for functional characterizations of their tumor-supportive roles in MM. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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16 pages, 2442 KiB  
Article
Interleukin-8 and Interleukin-6 Are Biomarkers of Poor Prognosis in Esophageal Squamous Cell Carcinoma
by Paula Roberta Aguiar Pastrez, Ana Margarida Barbosa, Vânia Sammartino Mariano, Rhafaela Lima Causin, Antonio Gil Castro, Egídio Torrado and Adhemar Longatto-Filho
Cancers 2023, 15(7), 1997; https://doi.org/10.3390/cancers15071997 - 27 Mar 2023
Cited by 1 | Viewed by 1366
Abstract
Esophageal squamous cell carcinoma (ESCC) is a common type of cancer characterized by fast progression and high mortality rates, which generally implies a poor prognosis at time of diagnosis. Intricate interaction networks of cytokines produced by resident and inflammatory cells in the tumor [...] Read more.
Esophageal squamous cell carcinoma (ESCC) is a common type of cancer characterized by fast progression and high mortality rates, which generally implies a poor prognosis at time of diagnosis. Intricate interaction networks of cytokines produced by resident and inflammatory cells in the tumor microenvironment play crucial roles in ESCC development and metastasis, thus influencing therapy efficiency. As such, cytokines are the most prominent targets for specific therapies and prognostic parameters to predict tumor progression and aggressiveness. In this work, we examined the association between ESCC progression and the systemic levels of inflammatory cytokines to determine their usefulness as diagnostic biomarkers. We analyzed the levels of IL-1β, IL-6, IL-8, IL-10, TNF-α e IL-12p70 in a group of 70 ESCC patients and 70 healthy individuals using Cytometric Bead Array (CBA) technology. We detected increased levels of IL-1β, IL-6, IL-8, and IL-10 in ESCC patients compared to controls. However, multivariate analysis revealed that only IL8 was an independent prognostic factor for ESCC, as were the well-known risk factors: alcohol consumption, tobacco usage, and exposure to pesticides/insecticides. Importantly, patients with low IL-6, IL-8, TNM I/II, or those who underwent surgery had a significantly higher overall survival rate. We also studied cultured Kyse-30 and Kyse-410 cells in mice. We determined that the ESCC cell line Kyse-30 grew more aggressively than the Kyse-410 cell line. This enhanced growth was associated with the recruitment/accumulation of intratumoral polymorphonuclear leukocytes. In conclusion, our data suggest IL-8 as a valuable prognostic factor with potential as a biomarker for ESCC. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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17 pages, 4038 KiB  
Article
The CXCL10/CXCR3 Pathway Contributes to the Synergy of Thermal Ablation and PD-1 Blockade Therapy against Tumors
by Wenlu Xiao, Hao Huang, Panpan Zheng, Yingting Liu, Yaping Chen, Junjun Chen, Xiao Zheng, Lujun Chen and Jingting Jiang
Cancers 2023, 15(5), 1427; https://doi.org/10.3390/cancers15051427 - 23 Feb 2023
Cited by 3 | Viewed by 1600
Abstract
As a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequency [...] Read more.
As a practical local therapeutic approach to destroy tumor tissue, thermal ablation can activate tumor-specific T cells via enhancing tumor antigen presentation to the immune system. In the present study, we investigated changes in infiltrating immune cells in tumor tissues from the non-radiofrequency ablation (RFA) side by analyzing single-cell RNA sequencing (scRNA-seq) data of tumor-bearing mice compared with control tumors. We showed that ablation treatment could increase the proportion of CD8+T cells and the interaction between macrophages and T cells was altered. Another thermal ablation treatment, microwave ablation (MWA), increased the enrichment of signaling pathways for chemotaxis and chemokine response and was associated with the chemokine CXCL10. In addition, the immune checkpoint PD-1 was especially up-regulated in the infiltrating T cells of tumors on the non-ablation side after thermal ablation treatment. Combination therapy of ablation and PD-1 blockade had a synergistic anti-tumor effect. Furthermore, we found that the CXCL10/CXCR3 axis contributed to the therapeutic efficacy of ablation combined with anti-PD-1 therapy, and activation of the CXCL10/CXCR3 signaling pathway might improve the synergistic effect of this combination treatment against solid tumors. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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19 pages, 7918 KiB  
Article
A Combined Risk Score Model to Assess Prognostic Value in Patients with Soft Tissue Sarcomas
by Zihua Li, Zhengwei Duan, Keyao Jia, Yiwen Yao, Kaiyuan Liu, Yue Qiao, Qiuming Gao, Yunfeng Yang, Guodong Li and Anquan Shang
Cells 2022, 11(24), 4077; https://doi.org/10.3390/cells11244077 - 16 Dec 2022
Cited by 2 | Viewed by 1498
Abstract
A study by Tsvetkov et al. recently published a proposed novel form of copper-induced cell death in Science; however, few studies have looked into the possible mechanism in soft tissue sarcoma (STS). Herein, this study sought to investigate the function of cuproptosis-related [...] Read more.
A study by Tsvetkov et al. recently published a proposed novel form of copper-induced cell death in Science; however, few studies have looked into the possible mechanism in soft tissue sarcoma (STS). Herein, this study sought to investigate the function of cuproptosis-related genes (CRGs) in the development of tumor-associated immune cells and the prognosis of sarcoma. Herein, this study aimed to explore the role of cuproptosis-related genes (CRGs) in the development, tumor-associated immune cells, and the prognosis of sarcoma. Methods: The prognostic model was established via the least absolute shrinkage and selection operator (LASSO) algorithm as well as multivariate Cox regression analysis. The stromal scores, immune scores, ESTIMA scores, and tumor purity of sarcoma patients were evaluated by the ESTIMATE algorithm. Functional analyses were performed to investigate the underlying mechanisms of immune cell infiltration and the prognosis of CRGs in sarcoma. Results: Two molecular subgroups with different CRG expression patterns were recognized, which showed that patients with a higher immune score and more active immune status were prone to have better prognostic survival. Moreover, GO and KEGG analyses showed that these differentially expressed CRGs were mainly enriched in metabolic/ions-related signaling pathways, indicating that CRGs may have impacts on the immune cell infiltration and prognosis of sarcoma via regulating the bioprocess of mitochondria and consequently affecting the immune microenvironment. The expression levels of CRGs were closely correlated to the immunity condition and prognostic survival of sarcoma patients. Conclusions: The interaction between cuproptosis and immunity in sarcoma may provide a novel insight into the study of molecular mechanisms and candidate biomarkers for the prognosis, resulting in effective treatments for sarcoma patients. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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15 pages, 2284 KiB  
Article
Clinical Value of Ultrasonography and Serum Markers in Preoperative N Staging of Thyroid Cancer
by Hui Wang, Shanshan Zhao, Chunyang Xu, Jincao Yao, Xiuhua Yu and Dong Xu
Cells 2022, 11(22), 3621; https://doi.org/10.3390/cells11223621 - 15 Nov 2022
Cited by 2 | Viewed by 1360
Abstract
We aimed to determine factors influencing lymph node metastasis (LNM) and develop a more effective method to assess preoperative N staging. Overall, data of 2130 patients who underwent thyroidectomy for thyroid cancer between 2018 and 2021 were retrospectively analysed. Patients were divided into [...] Read more.
We aimed to determine factors influencing lymph node metastasis (LNM) and develop a more effective method to assess preoperative N staging. Overall, data of 2130 patients who underwent thyroidectomy for thyroid cancer between 2018 and 2021 were retrospectively analysed. Patients were divided into groups according to pN0, pN1a, and pN1b stages. Pathology was used to analyse the correlation between preoperative serum marker indicators and LNM. Receiver operating characteristic curves were used to compare the diagnostic value of ultrasound (US) examination alone, serum thyroglobulin, age, and combined method for LNM. A significant moderate agreement was observed between preoperative US and postoperative pathology for N staging. Between the pN0 and pN1 (pN1a + pN1b) groups, the differences in free triiodothyronine, anti-thyroid peroxidase antibody, and serum thyroglobulin levels were statistically significant. Among the indicators, serum thyroglobulin was an independent predictor of LNM. The area under the receiver operating characteristic curve was 0.610 for serum thyroglobulin level for predicting LNM, 0.689 for US alone, and 0.742 for the combined method. Both preoperative US and serum thyroglobulin level provide a specific value when evaluating the N staging of thyroid cancer, and the combined method is more valuable in the diagnosis of LNM than US alone. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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20 pages, 2577 KiB  
Systematic Review
Focus on the Dynamics of Neutrophil-to-Lymphocyte Ratio in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis and Systematic Review
by Yusheng Guo, Dongqiao Xiang, Jiayu Wan, Lian Yang and Chuansheng Zheng
Cancers 2022, 14(21), 5297; https://doi.org/10.3390/cancers14215297 - 27 Oct 2022
Cited by 12 | Viewed by 2107
Abstract
Background: A number of studies have reported an association between the dynamics of neutrophil-to-lymphocyte ratio (NLR) and clinical efficacy in patients treated with immune checkpoint inhibitors (ICIs), but there is still a lack of a meta-analysis or systematic review. Methods: PubMed, Embase, Web [...] Read more.
Background: A number of studies have reported an association between the dynamics of neutrophil-to-lymphocyte ratio (NLR) and clinical efficacy in patients treated with immune checkpoint inhibitors (ICIs), but there is still a lack of a meta-analysis or systematic review. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched until September 2022 for studies reporting on the association between the change in NLR after ICI treatment and clinical outcomes. Outcome measures of interest included: change in NLR before and after treatment, overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of 4154 patients in 38 studies were included. The pooled percentage of patients with increased NLR was 49.7% (95CI%: 43.7–55.8%). Six studies discussing the change in NLR in patients with different tumor responses all showed that the NLR level in patients without response to immunotherapy may increase after ICI treatment. The upward trend in NLR was associated with shorter OS (pooled HR: 2.05, 95%CI: 1.79–2.35, p < 0.001) and PFS (pooled HR: 1.89, 95%CI: 1.66–2.14, p < 0.001) and higher ORR (pooled OR: 0.27, 95%CI: 0.19–0.39, p < 0.001), and downward trend in NLR was associated with longer OS (pooled HR: 0.49, 95%CI: 0.42–0.58, p < 0.001) and PFS (pooled HR: 0.55, 95%CI: 0.48–0.63, p < 0.001) and lower ORR (pooled OR: 3.26, 95%CI: 1.92–5.53, p < 0.001). In addition, post-treatment high NLR was associated with more impaired survival than baseline high NLR (pooled HR of baseline high NLR: 1.82, 95%CI: 1.52–2.18; pooled HR of post-treatment high NLR: 2.93, 95%CI: 2.26–3.81), but the NLR at different time points may have a similar predictive effect on PFS (pooled HR of baseline high NLR: 1.68, 95%CI: 1.44–1.97; pooled HR of post-treatment high NLR: 2.00, 95%CI: 1.54–2.59). Conclusions: The NLR level of tumor patients after ICI treatment is stable overall, but the NLR level in patients without response to immunotherapy may increase after ICI treatment. Patients with an upward trend in NLR after ICI treatment were associated with worse clinical outcomes; meanwhile, the downward trend in NLR was associated with better clinical outcomes. Post-treatment high NLR was associated with more impaired survival than baseline high NLR. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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17 pages, 19297 KiB  
Article
Inhibition of Autophagy Promotes the Anti-Tumor Effect of Metformin in Oral Squamous Cell Carcinoma
by Wei Zhao, Chen Chen, Jianjun Zhou, Xiaoqing Chen, Kuan Cai, Miaomiao Shen, Xuan Chen, Lei Jiang and Guodong Wang
Cancers 2022, 14(17), 4185; https://doi.org/10.3390/cancers14174185 - 29 Aug 2022
Cited by 7 | Viewed by 2072
Abstract
Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor in the head and neck. Due to its high malignancy and easy recurrence, the five-year survival rate is only 50–60%. Currently, commonly used chemotherapy drugs for OSCC include cisplatin, paclitaxel, and fluorouracil, [...] Read more.
Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor in the head and neck. Due to its high malignancy and easy recurrence, the five-year survival rate is only 50–60%. Currently, commonly used chemotherapy drugs for OSCC include cisplatin, paclitaxel, and fluorouracil, which are highly cytotoxic and cause drug resistance in patients. Therefore, a safe and effective treatment strategy for OSCC is urgent. To address this issue, our study investigated the anti-tumor activity of metformin (the first-line diabetes drug) in OSCC. We found that metformin could inhibit OSCC cell proliferation by promoting apoptosis and blocking the cell cycle in G1 phase. Additionally, we also found that metformin could induce protective autophagy of OSCC cells. After inhibiting autophagy with hydroxychloroquine (HCQ), the metformin-induced apoptosis was enhanced. In vitro, metformin inhibited the growth of subcutaneous xenograft tumor in nude mice and HCQ enhanced this effect of metformin. Therefore, metformin combined with HCQ may become a safe and effective treatment strategy for OSCC. Full article
(This article belongs to the Topic Inflammatory Tumor Immune Microenvironment)
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