bims-exocan 2022-11-20 papers

Issue of 2022–11–20
five papers selected by
Muhammad Rizwan, COMSATS University

Immune Netw. 2022 Oct;22(5): e38

Exosomal Communication Between the Tumor Microenvironment and Innate Immunity and Its Therapeutic Application.

Exosomes, which are well-known nanoscale extracellular vesicles, are multifunctional biomaterials derived from endosomes and perform various functions. The exosome is a critical material in cell-cell communication. In addition, it regulates the pathophysiological conditions of the tumor microenvironment in particular. In the tumor microenvironment, exosomes play a controversial role in supporting or killing cancer by conveying biomaterials derived from parent cells. Innate immunity is a crucial component of the host defense mechanism, as it prevents foreign substances, such as viruses and other microbes and tumorigenesis from invading the body. Early in the tumorigenesis process, the innate immunity explicitly recognizes the tumor via Ags and educates the adaptive immunity to eliminate it. Recent studies have revealed that exosomes regulate immunity in the tumor microenvironment. Tumor-derived exosomes regulate immunity against tumor progression and metastasis. Furthermore, tumor-derived exosomes regulate polarization, differentiation, proliferation, and activation of innate immune cells. Exosomes produced from innate immune cells can inhibit or support tumor progression and metastasis via immune cell activation and direct cancer inhibition. In this study, we investigated current knowledge regarding the communication between tumor-derived exosomes and innate immune cell-derived exosomes (from macrophages, dendritic cells, NK cells, and neutrophils) in the tumor microenvironment. In addition, we discussed the potential development of exosomal immunotherapy using native or engineered exosomes against cancer.

Keywords: Cancer; Exosomes; Innate immunity; Tumor microenvironment

DOI: https://doi.org/10.4110/in.2022.22.e38

Clin Exp Metastasis. 2022 Nov 16.

Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier.

Xin Liu, Yue Li, Chunjing Chen, Jiyang Dong, Jie Zhou, Dandan Tong, Lei Wang, Xiang Gao, Xinmei Kang.

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.

Keywords: Breast cancer; EphA2; Exosome; Tumor metastasis; Vascular permeability

DOI: https://doi.org/10.1007/s10585-022-10194-3

Front Oncol. 2022 ;12 1037523

Plasma exosomal tRNA-derived fragments as diagnostic biomarkers in non-small cell lung cancer.

Baibing Zheng, Xingguo Song, Li Wang, Yue Zhang, Youyong Tang, Shiwen Wang, Lei Li, Yawen Wu, Xianrang Song, Li Xie.

Background: tRNA derived small RNAs (tRFs) have recently received extensive attention; however, the effects of tRFs in exosome as biomarkers has been less studied. The objective of this study was to validate novel diagnostic exosomal tRFs with sensitivity and specificity for non-small cell lung cancer (NSCLC).
Methods: Exosomes extracted from plasma of NSCLC patients and healthy individuals were identified by transmission electron microscopy (TEM), qNano and western blots. The differentially expressed tRFs were screened by high-throughput sequencing in plasma exosomes of NSCLC patients and healthy individuals, and further verified by Quantitative Real-Time PCR (qRT-PCR). To assess the diagnostic efficacy of exosomal tRFs for NSCLC, receiver operating characteristic (ROC) curves were used next.
Results: The expression levels of exosomal tRF-Leu-TAA-005, tRF-Asn-GTT-010, tRF-Ala-AGC-036, tRF-Lys-CTT-049, and tRF-Trp-CCA-057 were significantly decreased in NSCLC patients and early-stage NSCLC patients compared to healthy individuals. Notably, the exepression of tRF-Leu-TAA-005, tRF-Asn-GTT-010, tRF-Ala-AGC-036, tRF-Lys-CTT-049, and tRF-Trp-CCA-057 in the exosomes were higher than the exosome depleted supernatant (EDS).
Conclusions: Our results showed that the levels of exosomal tRF-Leu-TAA-005, tRF-Asn-GTT-010, tRF-Ala-AGC-036, tRF-Lys-CTT-049, and tRF-Trp-CCA-057 were significantly downregulated in NSCLC patients. This suggests that these five exosomal tRFs may be promising diagnostic biomarkers for NSCLC.

Keywords: NSCLC; biomarker; diagnosis; exosomal tRFs; plasma

DOI: https://doi.org/10.3389/fonc.2022.1037523

Br J Cancer. 2022 Nov 16.

Large tumour-derived extracellular vesicles as prognostic indicators of metastatic cancer patient survival.

Deborah C I Goberdhan.

Extracellular vesicles (EVs) are released by all cells and produced at particularly high levels by many cancer cells, often inducing pro-tumorigenic effects. Since these cancer EVs carry tumour proteins and RNAs, they can potentially be used at biomarkers. The heterogeneity of surface markers and cargos carried by EVs, however, presents some challenges to developing such approaches. Nanou et al. [1] found that automated counting of large tumour-derived EVs (tdEVs) performed at least as effectively as counting circulating tumour-derived cells (CTCs) and with higher sensitivity, in distinguishing the survival of patients with castration-resistant prostate cancer (CRPC), metastatic colorectal cancer (mCRC) and metastatic breast cancer (MBC), but not for non-small cell lung cancer (NSCLC). Subsequent work has suggested that these tdEVs may also be used to assess tumour subtype and that the number of large EVs produced by endothelial cells can also be increased in cancer patients. While by itself, the tdEV imaging approach used by Nanou et al. [1] is not specific enough to predict the survival of individual patients, in combination with other EV-associated assays, this test, perhaps enhanced through the inclusion of other tumour antigens, could prove invaluable in predicting cancer survival and other outcomes in the clinic.

DOI: https://doi.org/10.1038/s41416-022-02055-3

Oncol Lett. 2022 Dec;24(6): 460

Potential of blood exosomal ENAH, SEPT9, EGF, MMP-9 and CXCL8 for the early screening of breast cancer.

Zijing Zhang, Hongying Wang, Yiting Jin, Chengyu Chu, Jinsong Bai, Juntian Huang, Lemei Yang, Feng Tang, Liping Zou, Shuyang Wang, Qiang Zou.

Exosomal contents have been recognized as candidate biomarkers for cancer screening and prognosis. The current study aimed to evaluate the potential of the expression levels of exosomal enabled homolog (ENAH), septin 9 (SEPT9), epidermal growth factor (EGF), matrix metalloproteinase-9 (MMP-9) and C-X-C motif chemokine ligand 8 (CXCL8) in the blood for the early screening of breast cancer. Therefore, exosomes were extracted and purified from the peripheral blood of 47 patients with breast cancer, 63 disease controls (DCs) and 33 healthy controls (HCs). Subsequently, the exosomal mRNA expression levels of ENAH, SEPT9, EGF, MMP-9 and CXCL8 were detected by reverse transcription-quantitative polymerase chain reaction. The results showed that the exosomal levels of ENAH and EGF were significantly higher in patients with breast cancer compared with DCs and HCs (both P<0.001). In addition, receiver operating characteristic curves revealed that exosomal ENAH was able to discriminate patients with breast cancer from DCs [area under the curve (AUC), 0.841] and HCs (AUC, 0.859). However, exosomal EGF was only able to discriminate patients with breast cancer from HCs (AUC, 0.776). Furthermore, the levels of exosomal SEPT9 were lower in patients with breast cancer compared with DCs and HCs (P=0.021), and exosomal SEPT9 expression levels exhibited good potential in the discrimination of patients with breast cancer from DCs (AUC, 0.717) and HCs (AUC, 0.830). However, no significant difference was detected in exosomal levels of MMP-9 and CXCL8 among the three groups, and these RNAs showed no discriminative ability. In addition, in patients with breast cancer, the exosomal levels of ENAH were associated with molecular subtypes (P=0.010), while those of MMP-9 were associated with a Ki-67 index of ≥30% (P=0.011). In conclusion, the exosomal levels of ENAH, SEPT9 and EGF in blood samples were able to identify patients with breast cancer, thus providing a novel approach for the early screening of breast cancer.

Keywords: breast cancer; early screening; exosomal EGF; exosomal ENAH; exosomal SEPT9

DOI: https://doi.org/10.3892/ol.2022.13580