Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours

Cheng, Yuanrong; Wang, Shou Bi; Liu, Jia Hui; Jin, Lin; Liu, Ying; Li, Chaoyang; Su, Ya; Liu, Yu Run; Sang, Xuan; Wan, Qi; Liu, Chang; Liu, Yang; Wang, Zhi Chong

doi:10.1111/cpr.12865

Cited by 69 publications

(44 citation statements)

References 183 publications

(365 reference statements)

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“… 208 Inhibition of the TGFβ signaling pathway in CAFs has been found to result in reduced collagen I secretion, resulting in reduced extracellular matrix stiffness. 209 Previous studies have shown that tumor resistance to ICP-targeting therapy was associated with a TGFβ signaling signature in fibroblasts. 208 , 210 Combining TGFβ-blockade with anti-PD-L1 antibodies has reduced TGFβ signaling in stromal cells, facilitated T-cell infiltration, and provoked vigorous antitumor immunity and tumor regression in a mouse model.…”

Section: Combined Time-targeted Therapy and Icp Inhibitor Treatmentmentioning

confidence: 99%

Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy

Tang

Huang

Zhang

et al. 2021

Sig Transduct Target Ther

285

197

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Despite great success in cancer immunotherapy, immune checkpoint-targeting drugs are not the most popular weapon in the armory of cancer therapy. Accumulating evidence suggests that the tumor immune microenvironment plays a critical role in anti-cancer immunity, which may result in immune checkpoint blockade therapy being ineffective, in addition to other novel immunotherapies in cancer patients. In the present review, we discuss the deficiencies of current cancer immunotherapies. More importantly, we highlight the critical role of tumor immune microenvironment regulators in tumor immune surveillance, immunological evasion, and the potential for their further translation into clinical practice. Based on their general targetability in clinical therapy, we believe that tumor immune microenvironment regulators are promising cancer immunotherapeutic targets. Targeting the tumor immune microenvironment, alone or in combination with immune checkpoint-targeting drugs, might benefit cancer patients in the future.

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Section: Combined Time-targeted Therapy and Icp Inhibitor Treatmentmentioning

confidence: 99%

Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy

Tang

Huang

Zhang

et al. 2021

Sig Transduct Target Ther

285

197

View full text Add to dashboard Cite

show abstract

“…These tumor-associated cells secrete soluble molecules and microvesicles that control the interactions of cancer cells with other cell types. This can influence how the tumor cells proliferate, oppose apoptosis, avoid elimination from the immune system, preserve stemness, invade, and metastasize ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

et al. 2020

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Treating individual patients on the basis of specific factors, such as biomarkers, molecular signatures, phenotypes, environment, and lifestyle is what differentiates the precision medicine initiative from standard treatment regimens. Although precision medicine can be applied to almost any branch of medicine, it is perhaps most easily applied to the field of oncology. Cancer is a heterogeneous disease, meaning that even though patients may be histologically diagnosed with the same cancer type, their tumors may have different molecular characteristics, genetic mutations or tumor microenvironments that can influence prognosis or treatment response. In this review, we describe what methods are currently available to clinicians that allow them to monitor key tumor microenvironmental parameters in a way that could be used to achieve precision medicine for cancer patients. We further describe exciting novel research involving the use of implantable medical devices for precision medicine, including those developed for mapping tumor microenvironment parameters (e.g., O 2 , pH, and cancer biomarkers), delivering local drug treatments, assessing treatment responses, and monitoring for recurrence and metastasis. Although these research studies have predominantly focused on and were tailored to humans, the results and concepts are equally applicable to veterinary patients. While veterinary clinical studies that have adopted a precision medicine approach are still in their infancy, there have been some exciting success stories. These have included the development of a receptor tyrosine kinase inhibitor for canine mast cell tumors and the production of a PCR assay to monitor the chemotherapeutic response of canine high-grade B-cell lymphomas. Although precision medicine is an exciting area of research, it currently has failed to gain significant translation into human and veterinary healthcare practices. In order to begin to address this issue, there is increasing awareness that cross-disciplinary approaches involving human and veterinary clinicians, engineers and chemists may be needed to help advance precision medicine toward its full integration into human and veterinary clinical practices.

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“…Although the acquisition of genetic mutations can drive therapeutic drug resistance mechanisms, another route by which resistance can emerge is through cell-cell communication within the heterogeneous tumour and with its stroma (Cheng et al, 2020). One evolutionarily conserved mechanism of intercellular signalling involves the transfer of extracellular vesicles (EVs) between cells (Meldolesi, 2018).…”

Section: Introductionmentioning

confidence: 99%

Anti-androgens induce Rab11a-exosome secretion in prostate cancer by suppressing amino acid-sensitive PAT4-mTORC1 signalling

McCormick

Sanitt

Fan

et al. 2020

Preprint

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Advanced prostate cancer is typically treated with anti-androgens to reduce cancer growth, but patients almost inevitably develop treatment resistance and castration-resistant disease. Recently, extracellular vesicles known as exosomes, which are secreted from the endosomal compartments in which they are formed, have been implicated in drug resistance mechanisms. Here we investigate whether growth regulation by the amino acid-dependent kinase complex, mechanistic Target of Rapamycin Complex 1 (mTORC1), and associated extracellular vesicle secretion might be involved in the adaptive responses to anti-androgens. We show that expression and intracellular localisation of the glutamine-sensing PAT4 (SLC36A4) amino acid transporter is increased in malignant versus benign prostatic tissue, mirroring earlier in vivo fly studies suggesting that these transporters are more effective at promoting growth from internal versus cell surface membranes. Furthermore, androgens induce PAT4 expression in prostate cancer cell lines and PAT4 is required for a proportion of androgen-stimulated mTORC1 activation and growth. Consistent with previous studies in other cancer cell lines, we find that glutamine depletion, PAT4 knockdown and mTORC1 inhibition all independently increase the production of a specific exosome subtype, Rab11a-exosomes, which has recently been implicated in pro-tumorigenic signalling responses to mTORC1 inhibition. Furthermore, we show that these exosomes are also induced by anti-androgens. We hypothesise that the uptake of Rab11a-exosomes by cells with higher PAT4 levels could provide a growth-promoting boost, enabling them to out-compete others with lower PAT4 expression, resulting in tumours that are more resistant to nutrient-deprivation and anti-androgen treatment.

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Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours

Cited by 69 publications

References 183 publications

Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy

Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology

Anti-androgens induce Rab11a-exosome secretion in prostate cancer by suppressing amino acid-sensitive PAT4-mTORC1 signalling

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