PD-1/PD-L1 blockade therapies provide notable clinical benefits for patients with advanced cancers, but the factors influencing the effectiveness of the treatment remain incompletely cataloged. Here, the up-regulation of laminin γ2 (Ln-γ2) predicted the attenuated efficacy of anti–PD-1 drugs and was associated with unfavorable outcomes in patients with lung cancer or esophageal cancer. Furthermore, Ln-γ2 was transcriptionally activated by transforming growth factor–β1 (TGF-β1) secreted from cancer-associated fibroblasts via JNK/AP1 signaling, which blocked T cell infiltration into the tumor nests by altering the expression of T cell receptors. Coadministration of the TGF-β receptor inhibitor galunisertib and chemotherapy drugs provoked vigorous antitumor activity of anti–PD-1 therapy in mouse tumor models. Therefore, Ln-γ2 may represent a useful biomarker to optimize clinical decisions and predict the response of cancer patients to treatment with anti–PD-1 drugs.

Sonodynamic therapy (SDT) is a promising new anti-tumor therapy that inhibits tumor growth by ultrasound activation of sonosensitizers to produce reactive oxygen species (ROS). However, the problems of hypoxia in the microenvironment within solid tumors and the effectiveness of SDT will decrease due to the little accumulation of sonosensitizers at the tumor site, as well as tumor cell tolerance, have limited the development of SDT. To overcome these problems, a core-shell structured nanoparticle (IR780/PLGA@MnO2 NPs) loaded with IR780 and manganese dioxide (MnO2) was developed as a nanocarrier to transport the sonosensitizer IR780 and the generated oxygen into the tumor tissue. The MnO2 shell layer of IR780/PLGA@MnO2 NPs can prevent the premature release of IR780 in the blood and also it can react with acidic and high H2O2, the generated oxygen can relieve tumor tissue hypoxia, and the generated Mn can enhance magnetic resonance imaging (MRI) signal intensity by acting as a contrast agent for MRI. More importantly, the released IR780 can produce ROS to kill tumor cells under ultrasound excitation. This PH-responsive and H2O2-triggered SDT based on the IR780/PLGA@MnO2NPs is an effective platform to inhibit tumor growth with negligible systemic toxicity. This work develops a multifunctional therapeutic integrated nanoplatform for breast cancer treatment, which is expected to be used in the clinic.

Background: Stemness acquirement is one of the hallmarks of cancer and the major reason for the chemoresistance and poor prognosis of colorectal cancer (CRC). Previous research has revealed the stimulatory role of paired related homeobox 1 (PRRX1) on CRC metastasis. However, the role of PRRX1 in stemness acquirement and chemoresistance of CRC is still not clear.Methods: A retrospective cohort study was performed to investigate the relationship between PRRX1 expression and multiple clinicopathological characteristics of CRC patients. The functional effects of PRRX1 on stemness and chemoresistance of CRC cells were validated by in vitro and in vivo assays. Gene set enrichment analysis (GSEA) and JASPAR software were performed to predict the underlying mechanisms.Enzyme-linked immunosorbent assay (ELISA), Western blot, immunofluorescence, and dual-luciferase reporter assays were used to confirm the PRRX1-mediated signaling and its downstream factors.Results: The expression of PRRX1 was up-regulated in CRC tissues and cell lines compared to normal epithelial tissues and cell lines. High expression of PRRX1 was tightly associated with the metastasis, chemoresistance, and poor prognosis of CRC patients. Additionally, PRRX1 significantly promoted the proliferation, viability, stemness, and chemoresistance of CRC cells, as well as the activation of the interleukin-6 (IL-6)/JAK2/STAT3 axis. Inhibiting the expression of IL-6 dramatically eliminated the effects of PRRX1 on CRC cell stemness and chemoresistance.Conclusions: PRRX1 plays a vital role in the stemness and chemoresistance of CRC cells via JAK2/ STAT3 signaling by targeting IL-6. Further, PRRX1 may be a valid biomarker for predicting the effect of chemotherapy and prognosis of CRC patients.

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Background: The aim of this study was to determine whether radiofrequency ablation (RFA) could activate immunity and slow non-ablated lesion growth in multifocal hepatic carcinoma.Methods: We performed a retrospective study on patients with multifocal hepatic carcinoma and assessed the non-ablated lesion growth rate between patients who received RFA and those who did not. In self-controlled study, before and three weeks after RFA, blood samples were collected from patients who received RFA to allow for comparisons of the alpha-fetoprotein (AFP) level, indoleamine 2,3-dioxygenase (IDO) concentration as assessed by enzyme-linked immunosorbent assay (ELISA) and IDO activity as assessed by high-performance liquid chromatography (HPLC).Results: A total of 66 patients were included in the retrospective analysis: there were 46 (69.7%) patients in the treatment group and 20 (30.3%) patients in the control group. The mean growth rate of non-ablated tumors was 0.0291 ± 0.0965 mm/d in the treatment group and 0.0947 ± 0.0754 mm/d in the control group (P = 0.001). The mean concentrations of IDO before and after RFA were 15.57±4.06 ng/ml and 7.53±1.56 ng/ml in 45 eligible patients, and this difference was significant (P = 0.034). The mean IDO activity values were 29.7±22.03 and 25.25±1.75 before and after RFA, respectively (P = 0.031). AFP decreased significantly after RFA, but there was no significant correlation between the decrease in AFP and the decrease in IDO concentration and activity.Conclusions: RFA may induce abscopal effects in hepatic carcinoma patients, manifested by a decrease in IDO concentration and activity and a slowed growth rate in non-ablated lesions.