Special Issue Topic
Cancer Immunotherapy and Tumor Microenvironment
Guest Editors
Dr. Fathia Mami-Chouaib E-Mail
INSERM UMR 1186, Integrative Tumour Immunology and Immunotherapy, Gustave Roussy, Fac. de Médecine - Univ. Paris-Sud, Université Paris-Saclay, 94805, Villejuif, France
Research Keywords: Onco-immunology; cancer immunotherapy; cancer vaccine; T lymphocytes; CTL; TRM
Dr. Salem Chouaib E-Mail
INSERM UMR 1186, Integrative Tumour Immunology and Immunotherapy, Gustave Roussy, Fac. de Médecine - Univ. Paris-Sud, Université Paris-Saclay, 94805, Villejuif, France; Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab Emirates
Research Keywords: Onco-immunology; tumor microenvironment; hypoxia; EMT; tumor immune escape
About the Special lssue
Immunotherapy is poised to become an increasingly used strategy for the treatment of cancer. Targeting immune checkpoints, such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), has led to unprecedented clinical outcomes in several cancer patients. However, despite the favorable outcome for immune checkpoint blockade (ICB)-responding patients, the response rate remains low. This is in part due to the influence of the tumor microenvironment (TME) in protecting malignant cells from the antitumor immune response and in facilitating immune escape. A paradoxical coexistence of tumor antigen-specific CD8 T lymphocytes and tumor growth arises from multiple negative immunoregulatory pathways that impede T cell-mediated tumor destruction. Indeed, cancer cells develop multiple immunosuppressive mechanisms to resist to antitumor immunity. The role of the tumor ecosystem during the initiation and progression of carcinogenesis is presently considered to be of critical importance. Therefore, targeting the TME-associated pathways may offer new options in the design of innovative cancer immunotherapy approaches. In this respect, immunotherapies could be more effective by combination of ICB and/or therapeutic cancer vaccines with agents that modulate the TME in order to overcome tumor tolerance and immune resistance, which are two major key issues that need more attention. This special issue aims to provide a comprehensive review covering some recent developments in the regulation of antitumor immunity and cancer immunotherapy, and the impact of the TME on tumor resistance and immune suppression. It also offers some perspectives on how exploring cancer cells that evade the immune surveillance may be helpful to develop more efficient strategies to target immune-escaped tumors and to design more adapted and integrative immunotherapies. The concept of reinvigorating the antitumor immune response by targeting the tumor ecosystem will certainly improve current cancer care.
Keywords: Onco-immunology; cancer immunotherapy; tumor microenvironment; T lymphocytes; MDSC; CAF; tumor resistance
Published Articles
Open Access
Perspective
Potential tactics with certain gut microbiota for the treatment of unresectable hepatocellular carcinoma
Hepatocellular carcinoma (HCC) constitutes an extremely malignant form of primary liver cancer. Intricate connections linking to the immune system might be associated with the pathogenesis of HCC. M
Published: August 24, 2023 Explor Target Antitumor Ther. 2023;4:556–568
Open Access
Perspective
Potential tactics with vitamin D and certain phytochemicals for enhancing the effectiveness of immune-checkpoint blockade therapies
Immunotherapy strategies targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) are revolutionizing oncology. However,
Published: June 30, 2023 Explor Target Antitumor Ther. 2023;4:460–473
Open Access
Review
Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy
Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized.
Published: April 28, 2023 Explor Target Antitumor Ther. 2023;4:316–343
Open Access
Review
Gut microbiota, an emergent target to shape the efficiency of cancer therapy
It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer throu
Published: April 26, 2023 Explor Target Antitumor Ther. 2023;4:240–265
Open Access
Review
Cancer resistance via the downregulation of the tumor suppressors RKIP and PTEN expressions: therapeutic implications
The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and me
Published: April 20, 2023 Explor Target Antitumor Ther. 2023;4:170–207
Open Access
Perspective
A primer on cancer-associated fibroblast mechanics and immunosuppressive ability
Cancer-associated fibroblasts (CAFs) are a major point of interest in modern oncology. Their interest resides in their ability to favor tumor growth without carrying genetic mutations. From a transl
Published: February 20, 2023 Explor Target Antitumor Ther. 2023;4:17–27
Open Access
Review
New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme
Glioblastoma multiforme (GBM) is known as the most aggressive and prevalent brain tumor with a high mortality rate. It is reported in people who are as young as 10 years old to as old as over 70 years old, exhibiting inter and intra tumor heterogeneity. There are several genomic and proteomic investigations that have been performed to find the unexplored potential targets of the drug against GBM. Therefore, certain effective targets have been taken to further validate the studies embarking on the robustness in the field of medicinal chemistry followed by testing in clinical trials. Also, The Cancer Genome Atlas (TCGA) project has identified certain overexpressed targets involved in the pathogenesis of GBM in three major pathways, i.e., tumor protein 53 (p53), retinoblastoma (RB), and receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathways. This review focuses on the compilation of recent developments in the fight against GBM thus, directing future research into the elucidation of pathogenesis and potential cure for GBM. Also, it highlights the potential biomarkers that have undergone extensive research and have promising prognostic and predictive values. Additionally, this manuscript analyses the advent of gene therapy and immunotherapy, unlocking the way to consider treatment approaches other than, or in addition to, conventional chemo-radiation therapies. This review study encompasses all the relevant research studies associated with the pathophysiology, occurrence, diagnostic tools, and therapeutic intervention for GBM. It highlights the evolution of various therapeutic perspectives against GBM from the most conventional form of radiotherapy to the recent advancement of gene/cell/immune therapy. Further, the review focuses on various targeted therapies for GBM including chemotherapy sensitization, radiotherapy, nanoparticles based, immunotherapy, cell therapy, and gene therapy which would offer a comprehensive account for exploring several facets related to GBM prognostics.
Published: December 30, 2022 Explor Target Antitumor Ther. 2022;3:866–888
Open Access
Original Article
Evaluating immune response in vitro in a relevant microenvironment: a high-throughput microfluidic model for clinical screening
Aim: Functional screening of new pharmaceutical compounds requires clinically relevant models to monitor essential cellular and immune responses during cancer progression, with or without treatment. Beyond survival, the emergence of resistant tumor cell clones should also be considered, including specific properties related to plasticity, such as invasiveness, stemness, escape from programmed cell death, and immune response. Numerous pathways are involved in these processes. Defining the relevant ones in the context of a specific tumor type will be key to designing an appropriate combination of inhibitors. However, the diversity and potential redundancy of these pathways remain a challenge for therapy.
Methods: A new microfluidic device developed by Okomera was dedicated to the screening of drug treatment for breast cancer. This microchip includes 150 droplet-trapping microwells, offering multi-chip settings and multiple treatment choices.
Results: After validating the system with established cell lines and a panel of drugs used clinically at Gustave Roussy, preclinical experiments were initiated including patient-derived xenograft (PDX) and primary tumor cells-derived tumoroids with the collaboration of Gustave Roussy clinicians. Tumor-isolated lymphocytes were also added to the tumoroids, using secondary droplets in proof-of-concept experiments.
Conclusions: These results show the relevance of the methodology for screening large numbers of drugs, a wide range of doses, and multiple drug combinations. This methodology will be used for two purposes: 1) new drug screening from the compound library, using the high throughput potential of the chip; and 2) pre-clinical assay for a two-weeks response for personalized medicine, allowing evaluation of drug combinations to flag an optimized treatment with potential clinical application.
Published: December 29, 2022 Explor Target Antitumor Ther. 2022;3:853–865
Open Access
Original Article
Dendritic cell-targeting chemokines inhibit colorectal cancer progression
Aim:
Recent progress in cancer immunotherapy has shown its promise and prompted researchers to develop novel therapeutic strategies. Dendritic cells (DCs) are professional antigen-presenting cell
Published: December 27, 2022 Explor Target Antitumor Ther. 2022;3:828–840
Open Access
Review
Mutant and non-mutant neoantigen-based cancer vaccines: recent advances and future promises
Major advances in cancer treatment have emerged with the introduction of immunotherapies using blocking antibodies that target T-cell inhibitory receptors, such as programmed death-1 (PD-1) and cyto
Published: December 22, 2022 Explor Target Antitumor Ther. 2022;3:746–762
Open Access
Review
The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors
Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has
Published: October 31, 2022 Explor Target Antitumor Ther. 2022;3:694–718
Open Access
Review
Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions
Cancer-associated fibroblasts (CAFs) are highly heterogeneous players that shape the tumor microenvironment and influence tumor progression, metastasis formation, and response to conventional therap
Published: October 27, 2022 Explor Target Antitumor Ther. 2022;3:598–629
Open Access
Review
Myeloid-derived suppressor cells in colorectal cancer: prognostic biomarkers and therapeutic targets
Myeloid-derived suppressor cells (MDSCs) are a group of immature myeloid cells, which are expanded in most cancer patients. MDSCs suppress host immune responses, leading to cancer growth and progres
Published: August 31, 2022 Explor Target Antitumor Ther. 2022;3:497–510
Ongoing Special Issues
The Role of Bcl-2 Family Proteins in Cancer Progression and Their Relevance to Cancer Therapy
Innovative Strategies to Target Triple-negative Breast Cancer
Novel Insights into Immunotherapy Targeting Tumor Microenvironment in Cancer
Current Innovative Cancer Treatment
Molecular Diagnosis and Personalized Therapy of Cancer
Immunotherapy Strategies for Non-small Cell Lung Cancer
Advances in Cancer Genomics and Therapeutic Targets
Comprehensive Immunotherapy of Solid Tumors
Posttranslational Modifications in Health and Disease
Novel Biomarkers in the Immunotherapy Era
Mechanisms of Targeted Therapy Resistance and Reversal Strategies
Immune Checkpoint Therapy and Biomarkers in Cancer
Cancer Epigenetics: Implications for Novel Therapeutic Strategies
Predictive and Prognostic Biomarkers in Cancer: Towards the Precision Medicine Era
Potential Clinical Applications of Inorganic Nanomaterials in Cancer
Use of Different Radiation Treatment Modalities in Cancer Therapy: The Role of Inflammation and Immune Response
Molecular Mechanisms and Intervention Options in Metastatic Spread of Cancer
Potential of Non-Coding RNAs in Cancer Research and Treatment
Liquid Biopsy: Has Already Changed the Clinical Decision-Making in Solid Tumors Treatment?
Artificial Intelligence Technology in Tumor Radiotherapy
Completed Special Issues
Liquid Biopsy in Thoracic Cancer
Targeting Transcription Factors for Cancer Therapy
Immunotherapy in Cancer Patients
Calcium Signaling Apparatus in Cancers
Off-Label Drugs and -Omics Data in Cancer Treatment
COVID-19 and Cancer
Proteolysis Targeting Chimera (PROTAC)
Precision Medicine for Cholangiocarcinoma
Antibody-Drug Conjugates
Endocrine Resistant Breast Cancer
Gene Delivery Approach to Fight Cancer
The Implementation of Liquid Biopsy in Clinical Practice for Different Solid Tumor
Cancer Immunotherapy and Tumor Microenvironment
Theranostic Frontiers in Neuro-Oncology
Plant Extracts as an Infinite Resource for New Anticancer Agents
Biomarkers for Personalized and Precise Cancer Diagnosis and Treatment
Artificial Intelligence for Precision Oncology
Therapeutic Targeting of the Tumor Microenvironment
Novel Strategies and Targets for Immunotherapy of Cancer
Integrated Approaches for Non-Small-Cell Lung Cancer
Emerging Molecular Targets and Therapies of Genitourinary Tumors