Immunity beyond cancer cells: perspective from tumor tissue

Gao, Shengyu; Hsu, Thomas T. C.; Li, Ming O.

doi:10.1016/j.trecan.2021.06.007

Cited by 27 publications

(15 citation statements)

References 85 publications

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“…In this study, we found that the PTX-JG combination improved the level of CD3 + and CD4 + T cells and maintained the CD4+/ CD8+ immune balance despite the unobvious immuneenhancement effect of using JG alone. According to the data of secretion of cytokines, CD4 + T cells and CD4+/ CD8+ ratio in the experiment, we speculate that the improvement of body immunity may also be one of the main causes for the improvement of anticancer effect of the PTX-JG combination group (Chen and Musa, 2021;Gao et al, 2021).…”

Section: Discussionmentioning

confidence: 81%

Jiegeng Decoction Potentiates the Anticancer Efficacy of Paclitaxel in vivo and in vitro

Chen

Liu

et al. 2022

Front. Pharmacol.

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Paclitaxel (PTX) has been the first-line treatment for lung cancer; however, its clinical use is limited due to multidrug resistance (MDR) and adverse effects. Thus, there is an urgent need to explore agents that can enhance the anticancer efficacy of PTX by reducing drug resistance and adverse reactions. Jiegeng decoction (JG) was used as the meridian guide drug and adjuvant drug in treatment of lung cancer. However, the mechanism of adjuvant effect was unclear. The aim of this study was to determine whether JG could potentiate the anticancer effect of PTX. Tissue distribution of PTX was detected using HPLC-MS/MS. The anti-lung cancer effect of the combination of PTX and JG in Lewis lung cancer C57BL/6J mice was evaluated based on the body weight and tumor-inhibition rate. PTX concentration in tumors was determined using HPLC-MS and in vivo imaging. Biochemical indices were detected using biochemical analyzer and ELISA. The anticancer mechanism of the PTX-JG combination in A549/PTX cells was elucidated based on cell proliferation, annexin V-FITC apoptosis assay, and western blotting. Tissue distribution analysis showed that the distribution of PTX increased in the lungs, liver, and heart upon administering the combination of PTX and JG. JG remarkably enhanced the anticancer effect of PTX by increasing the red blood cell and platelet counts; increasing hemoglobin, interleukin (IL)-2, and tumor necrosis factor-α levels; increasing CD4+T cells and the CD4+/CD8+ ratio; and decreasing IL-10 levels. JG administration led to the increased distribution of PTX at the tumor lesion sites and also potentiated the anticancer effect of PTX by inhibiting tumor cell proliferation and promoting apoptosis. Moreover, JG reversed PTX resistance by inhibiting the expression of lung resistance-related proteins, multiresistance protein 1, P-glycoprotein, and breast cancer-resistant protein. Furthermore, the combination of JG and PTX decreased alanine aminotransferase and aspartate aminotransferase levels and did not affect creatine kinase-MB levels. Therefore, our discovery suggests that JG increased the anticancer effect of PTX by downregulating the MDR-related protein and demonstrated a synergistic enhancement of immunity. Thus, the combination of PTX with JG shows potential in the management of lung cancer owing to its synergistic and detoxifying effects.

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Section: Discussionmentioning

confidence: 81%

Jiegeng Decoction Potentiates the Anticancer Efficacy of Paclitaxel in vivo and in vitro

Chen

Liu

et al. 2022

Front. Pharmacol.

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“…In addition, CD8 + T cells can secrete cytotoxic particles, making them a type of cytotoxic cell that plays an important role in antitumor immunity ( 33 , 34 ). On the other hand, PDSS1 is significantly positively correlated with Th2 cells, TFH, and T helper cells, and they play an important role in regulating tumor immunity ( 35 – 37 ). In summary, the above results indicates that PDSS1 plays an important role in regulating immune cell infiltration in HCC.…”

Section: Discussionmentioning

confidence: 99%

A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC

Rao

Yao

et al. 2022

Front. Oncol.

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Decaprenyl diphosphate synthase subunit 1 (PDSS1) is closely related to a variety of human diseases, but its expression pattern and biological function in HCC have not been studied to date.MethodsThe expression level of PDSS1 was analyzed using the TCGA and GEO databases. The relationships between PDSS1 and patient clinicopathological characteristics were verified based on TCGA clinical data. Additionally, the co-expressed genes of PDSS1were investigated and Gene Set Enrichment Analysis (GSEA) was conducted using LinkedOmics. Next, the association between PDSS1 and immune infiltration was determined using version 1.34.0 of the GSVA package. EdU assay, colony-formation assay, transwell assay, wound-healing assay, and flow cytometry analysis were used to assess the effect of PDSS1 on the cell phenotype.ResultsPDSS1 was upregulated in HCC compared with adjacent tissues. High PDSS1 in HCC was associated with poor overall survival, disease-specific survival, and progress-free interval. Results suggested that PDSS1 may activate multiple oncogenic pathways in HCC, especially those involved in the cell cycle. The expression of PDSS1 was significantly related to Th2 cells, TFH, T helper cells, NK CD56bright cells, cytotoxic cells, DC, CD8 T cells, and neutrophils. PDSS1 knockdown inhibited cell proliferation, cell cycle, migration and invasion. Furthermore, PDSS1 acted as an oncogene through the STAT3 signaling pathway.ConclusionOur study reveals that a high level of PDSS1 is significantly correlated with poor patient prognosis and immune cell infiltration in HCC. PDSS1 may be a novel biomarker and potential therapeutic target for HCC.

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“…It has been shown that Tfh cells can drive resident CXCR5 effector T cells to produce Th1-directed responses in active TLS (67). Th1 is the most detected Th cell subset in non-cancerous tissues, and Th2, which is widely detected in patients with a poor prognosis, is considered to have a cancer-promoting effect (68)(69)(70). Th1 cells may be related to the initiation and/or maintenance of local and systemic adaptive immune responses while protecting patients from tumor invasion and metastasis (71).…”

Section: Role Of Itls In Phcmentioning

confidence: 99%

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope

et al. 2022

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Tertiary lymphoid structures (TLSs) are organized aggregates of immune cells found in the tumor microenvironment. TLS can influence primary hepatic carcinoma (PHC) occurrence and have an active role in cancer. TLS can promote or inhibit the growth of PHC depending on their location, and although available findings are controversial, they suggest that TLS have a protective role in PHC tissues and a non-protective role in paracancerous tissues. In addition, the cellular composition of TLS can also influence the outcome of PHC. As an immunity marker, TLS can act as a marker of immunotherapy to predict its effect and help to identify patients who will respond well to immunotherapy. Modulation of TLS formation through the use of chemokines/cytokines, immunotherapy, or induction of high endothelial vein to interfere with tumor growth has been studied extensively in PHC and other cancers. In addition, new tools such as genetic interventions, cellular crosstalk, preoperative radiotherapy, and advances in materials science have been shown to influence the prognosis of malignant tumors by modulating TLS production. These can also be used to develop PHC treatment.

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Immunity beyond cancer cells: perspective from tumor tissue

Cited by 27 publications

References 85 publications

Jiegeng Decoction Potentiates the Anticancer Efficacy of Paclitaxel in vivo and in vitro

Jiegeng Decoction Potentiates the Anticancer Efficacy of Paclitaxel in vivo and in vitro

A novel HCC prognosis predictor PDSS1 affects the cell cycle through the STAT3 signaling pathway in HCC

Tertiary Lymphatic Structures in Primary Hepatic Carcinoma: Controversy Cannot Overshadow Hope

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