Revealing the crucial roles of suppressive immune microenvironment in cardiac myxoma progression

Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening.However,the cellular composition of this condition is still not well understood.To fill this gap,we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing.We defined a population of myxoma cells,which exhibited a resemblance to fibroblasts,yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation,differentiation,and adhesion.The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration,along with their enhanced spatial interaction,were found to significantly contribute to the occurrence of embolism.The immune cells surrounding the myxoma exhibit inhibitory characteristics,with impaired function of T cells characterized by the expression of GZMK and TOX,along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC.Furthermore,in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly.In summary,this study presents a comprehensive single-cell atlas of cardiac myxoma,highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells.These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.

Signaling Pathways Associated with Cancer Stem Cells Play a Significant Role in Immunotherapy Resistance

Cancer stem cells(CSCs)are a subpopulation of tumor cells with properties of self-renewal,pluripotency,plasticity,and differentiation,and are associated with various aberrantly stimulated signaling pathways.They are responsible for tumor recurrence,distant metastasis,and drug resistance,thus inducing poor prognosis.Immunotherapy has achieved encouraging results.However,the resistance associated with its clinical application is a persistent problem in clinical and scientific researches.Increasing evidence shows that signaling pathways associated with CSCs mediate immunotherapy resistance.This review highlights the link between them,and focuses on the underlying mechanism so as to provide potential strategies and approaches for the development of new targets against the immune resistance challenge.

Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis

The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer.However,cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues.Here,we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples,including blood,normal tissue,para-cancer,polyp,and colorectal cancer.

Polymeric dual-modal imaging nanoprobe with two-photon aggregation-induced emission for fluorescence imaging and gadolinium-chelation for magnetic resonance imaging

Nanoprobes that offer both fluorescence imaging(FI)and magnetic resonance imaging(MRI)can provide supplementary information and hold synergistic advantages.However,synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups,high stability,great biocompatibility and desired dual-modality imaging results remains challenging.In this study,we used an amphiphilic block polymer from(ethylene glycol)methyl ether methacrylate(OEGMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)derivatives as a carrier to conjugate a MR contrast agent,Gd-DOTA,and a two-photon fluorophore with an aggregation-induced emission(AIE)effect,TPBP,to construct a MR/two-photon fluorescence dual-modality contrast agent,Gd-DOTA-TPBP.Incorporation of gadolinium in the hydrophilic chain segment of the OEGMA-based carrier resulted in a high r_(1)value for Gd-DOTA-TPBP,revealing a great MR imaging resolution.The contrast agent specifically accumulated in the tumor region,allowing a long enhancement duration for vascular and tumor contrast-enhanced MR imaging.Meanwhile,coupling TPBP with AIE properties to the hydrophobic chain segment of the carrier not only improved its water solubility and reduced its cytotoxicity,but also significantly enhanced its imaging performance in an aqueous phase.Gd-DOTA-TPBP was also demonstrated to act as an excellent fluorescence probe for two-photon-excited bioimaging with higher resolution and greater sensitivity than MRI.Since high-resolution,complementary MRI/FI dual-modal images were acquired at both cellular and tissue levels in tumor-bearing mice after application of Gd-DOTA-TPBP,it has great potential in the early phase of disease diagnosis.

Corrigendum to “A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody” [Bioact. Mater. 21 299-312]

The authors regret the incorrect publication of corresponding authors for the article.The corresponding authors have been updated as Hongyan Zhu(hyzhu_hmrrc@126.com)and Kui Luo(luokui@scu.edu.cn),and the same should be updated in the supplementary file as well.

Expert consensus on the diagnosis and treatment of solid tumors with BRAF mutations

The BRAF gene is an important signaling molecule in human cells that is involved in the regulation of cell growth,differentiation,and survival.When the BRAF gene mutates,it can lead to abnormal activation of the signaling pathway,which promotes cell proliferation,inhibits cell apoptosis,and ultimately contributes to the occurrence and development of cancer.BRAF mutations are widely present in various cancers,including malignant melanoma,thyroid cancer,colorectal cancer,non-small cell lung cancer,and hairy cell leukemia,among others.BRAF is an important target for the treatment of various solid tumors,and targeted combination therapies,represented by BRAF inhibitors,have become one of the main treatment modalities for a variety of BRAF-mutation-positive solid tumors.

The role of lysosome in regulated necrosis

Lysosome is a ubiquitous acidic organelle fundamental for the turnover of unwanted cellular molecules,particles,and organelles.Currently,the pivotal role of lysosome in regulating cell death is drawing great attention.Over the past decades,we largely focused on how lysosome influences apoptosis and autophagic cell death.However,extensive studies showed that lysosome is also prerequisite for the execution of regulated necrosis(RN).Different types of RN have been uncovered,among which,necroptosis,ferroptosis,and pyroptosis are under the most intensive investigation.It becomes a hot topic nowadays to target RN as a therapeutic intervention,since it is important in many patho/physiological settings and contributing to numerous diseases.It is promising to target lysosome to control the occurrence of RN thus altering the outcomes of diseases.Therefore,we aim to give an introduction about the common factors influencing lysosomal stability and then summarize the current knowledge on the role of lysosome in the execution of RN,especially in that of necroptosis,ferroptosis,and pyroptosis.

Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials

Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence.Epigenetic dysregulation is often linked to human disease,notably cancer.With the development of various drugs targeting epigenetic regulators,epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials.In this review,we summarize the aberrant functions of enzymes in DNA methylation,histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes.

A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosup-pressive cancers like triple-negative breast cancer(TNBC),induction of immunogenic cell death(ICD)at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors.Herein,a self-amplified biomimetic nanosystem,mEHGZ,was constructed by encapsulation of epirubicin(EPI),glucose oxidase(Gox)and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin(CRT)over-expressed tumor cell mem-brane.EPI acts as an ICD inducer,Gox and hemin medicate the cascade generation of reactive oxygen species(ROS)to strengthen the ICD effect,and CRT-rich membrane as“eat me”signal promote presentation of the released antigens by dendritic cells(DCs)to invoke the tumor-immunity cycle.The biomimetic delivery system displays an amplified ICD effect via Gox oxidation,hydroxyl radical generation and glutathione(GSH)depletion.The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes(CTLs)infiltration,reversing an immunosuppressive tumor microenvironment to an immunoresponsive one.Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis,supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody.This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

阻断循环肿瘤细胞免疫检查点HLA-E:CD94-NKG2A抑制肿瘤转移

肿瘤细胞的转移扩散是癌症相关死亡的主要原因.从原发灶肿瘤脱落的循环肿瘤细胞(circulating tumor cells,CTCs)被认为是肿瘤远端转移的“种子”[1].阐明肿瘤细胞转移扩散的潜在机制、开发针对肿瘤转移“种子”细胞的新型治疗策略对抑制肿瘤转移具有重要意义.近年来,随着人们对肿瘤免疫逃逸的认知,实体肿瘤原发或转移灶肿瘤微环境中肿瘤细胞与不同类型的免疫细胞之间的免疫检查点分子已经得到了广泛的研究,并被应用于肿瘤的临床治疗.其中,以PD-1/PD-L1和CTLA4为代表的免疫检查点阻断疗法彻底改变了多种癌症的治疗模式[2,3].由于血液循环是肿瘤细胞从原发灶向远端转移的主要途径[4],研究CTCs与血液中免疫细胞之间的相互作用可能提供一种通过激活宿主免疫系统来阻断转移的策略.然而,目前关于CTCs在血液中如何逃脱宿主免疫监视的机制尚不清楚,也缺乏有效的抑制CTCs转移扩散的治疗方案.

Targeted therapy for head and neck cancer:signaling pathways and clinical studies

Head and neck cancer(HNC)is malignant,genetically complex and difficult to treat and is the sixth most frequent cancer,with tobacco,alcohol and human papillomavirus being major risk factors.Based on epigenetic data,HNC is remarkably heterogeneous,and treatment remains challenging.There is a lack of significant improvement in survival and quality of life in patients with HNC.Over half of HNC patients experience locoregional recurrence or distal metastasis despite the current multiple traditional therapeutic strategies and immunotherapy.In addition,resistance to chemotherapy,radiotherapy and some targeted therapies is common.Therefore,it is urgent to explore more effective and tolerable targeted therapies to improve the clinical outcomes of HNC patients.Recent targeted therapy studies have focused on identifying promising biomarkers and developing more effective targeted therapies.A well understanding of the pathogenesis of HNC contributes to learning more about its inner association,which provides novel insight into the development of small molecule inhibitors.In this review,we summarized the vital signaling pathways and discussed the current potential therapeutic targets against critical molecules in HNC,as well as presenting preclinical animal models and ongoing or completed clinical studies about targeted therapy,which may contribute to a more favorable prognosis of HNC.Targeted therapy in combination with other therapies and its limitations were also discussed.

Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection

The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection.