Key Players of the Immunosuppressive Tumor Microenvironment and Emerging Therapeutic Strategies

Park, Kevin; Veena, Mysore S.; Shin, Daniel Sanghoon

doi:10.3389/fcell.2022.830208

Cited by 19 publications

(11 citation statements)

References 249 publications

(287 reference statements)

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“…DCs not only have antigen presentation function, but also have anticancer effects by stimulating a large number of exosomes ( 231 ). DC-derived exosomes contain MHC I, MHC II, CD86, and HSP70–90 mixtures, which activate CD4+ and CD8+ T cells ( 232 ). In vivo , tumor peptide-pulsed DC-derived exosomes have been shown to induce specific cytotoxicity of T cells and inhibit or eradicate mouse tumor cell growth in a T-cell-dependent manner.…”

Section: Roles Of Exosomes In the Tmementioning

confidence: 99%

Exosomes: A potential tool for immunotherapy of ovarian cancer

et al. 2023

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Ovarian cancer is a malignant tumor of the female reproductive system, with a very poor prognosis and high mortality rates. Chemotherapy and radiotherapy are the most common treatments for ovarian cancer, with unsatisfactory results. Exosomes are a subpopulation of extracellular vesicles, which have a diameter of approximately 30–100 nm and are secreted by many different types of cells in various body fluids. Exosomes are highly stable and are effective carriers of immunotherapeutic drugs. Recent studies have shown that exosomes are involved in various cellular responses in the tumor microenvironment, influencing the development and therapeutic efficacy of ovarian cancer, and exhibiting dual roles in inhibiting and promoting tumor development. Exosomes also contain a variety of genes related to ovarian cancer immunotherapy that could be potential biomarkers for ovarian cancer diagnosis and prognosis. Undoubtedly, exosomes have great therapeutic potential in the field of ovarian cancer immunotherapy. However, translation of this idea to the clinic has not occurred. Therefore, it is important to understand how exosomes could be used in ovarian cancer immunotherapy to regulate tumor progression. In this review, we summarize the biomarkers of exosomes in different body fluids related to immunotherapy in ovarian cancer and the potential mechanisms by which exosomes influence immunotherapeutic response. We also discuss the prospects for clinical application of exosome-based immunotherapy in ovarian cancer.

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Section: Roles Of Exosomes In the Tmementioning

confidence: 99%

Exosomes: A potential tool for immunotherapy of ovarian cancer

et al. 2023

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“…Targeting the chemokine receptor CXCR2 can reduce MDSC populations, promote T-cell infiltration, and improve the efficacy of PD-1 blockade in preclinical studies [ 245 , 246 ]. SX-682, a CXCR1/2 inhibitor, enhanced the T-cell-based immunotherapeutic efficacy in studies using murine tumor models that assessed MDSC-infiltration [ 247 , 248 ]. The CXCR1/2 inhibitor reparixin showed promise in a window-of-opportunity clinical trial for HER-2-negative breast cancer.…”

Section: Inhibition Of Mdsc Recruitmentmentioning

confidence: 99%

Role of myeloid-derived suppressor cells in tumor recurrence

Cole

Al-Kadhimi

Talmadge

2023

Cancer Metastasis Rev

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The establishment of primary tumor cells in distant organs, termed metastasis, is the principal cause of cancer mortality and is a crucial therapeutic target in oncology. Thus, it is critical to establish a better understanding of metastatic progression for the future development of improved therapeutic approaches. Indeed, such development requires insight into the timing of tumor cell dissemination and seeding of distant organs resulting in occult lesions. Following dissemination of tumor cells from the primary tumor, they can reside in niches in distant organs for years or decades, following which they can emerge as an overt metastasis. This timeline of metastatic dormancy is regulated by interactions between the tumor, its microenvironment, angiogenesis, and tumor antigen-specific T-cell responses. An improved understanding of the mechanisms and interactions responsible for immune evasion and tumor cell release from dormancy would help identify and aid in the development of novel targeted therapeutics. One such mediator of dormancy is myeloid derived suppressor cells (MDSC), whose number in the peripheral blood (PB) or infiltrating tumors has been associated with cancer stage, grade, patient survival, and metastasis in a broad range of tumor pathologies. Thus, extensive studies have revealed a role for MDSCs in tumor escape from adoptive and innate immune responses, facilitating tumor progression and metastasis; however, few studies have considered their role in dormancy. We have posited that MDSCs may regulate disseminated tumor cells resulting in resurgence of senescent tumor cells. In this review, we discuss clinical studies that address mechanisms of tumor recurrence including from dormancy, the role of MDSCs in their escape from dormancy during recurrence, the development of occult metastases, and the potential for MDSC inhibition as an approach to prolong the survival of patients with advanced malignancies. We stress that assessing the impact of therapies on MDSCs versus other cellular targets is challenging within the multimodality interventions required clinically.

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“…TME is composed of tumor cells, immune cells, stromal cells, extracellular matrix, and exosomes ( 4 ), thus forming a microenvironment with the characteristics of inflammation, hypoxia, acidity, and immunosuppression. Different types of cells in TME have their preferred metabolic phenotypes ( Figure 1 ).…”

Section: Characteristics and Classifications Of Tmementioning

confidence: 99%

PET/CT molecular imaging in the era of immune-checkpoint inhibitors therapy

Gao

Chen

et al. 2022

Front. Immunol.

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Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of 18F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.

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Key Players of the Immunosuppressive Tumor Microenvironment and Emerging Therapeutic Strategies

Cited by 19 publications

References 249 publications

Exosomes: A potential tool for immunotherapy of ovarian cancer

Exosomes: A potential tool for immunotherapy of ovarian cancer

Role of myeloid-derived suppressor cells in tumor recurrence

PET/CT molecular imaging in the era of immune-checkpoint inhibitors therapy

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