Efficacy, cardiotoxicity and factors affecting pathologic complete response of neoadjuvant chemotherapy with anthracycline-containing verses anthracycline-free regimens plus dual HER2 blockade for HER2-positive early-stage breast cancer: a retrospective study.

Background: The aim of this study was to compare the efficacy, cardiotoxicity and factors affecting pathologic complete response (pCR) of neoadjuvant chemotherapy (NACT) regimen TCbHP (docetaxel/nab-paclitaxel, carboplatin, trastuzumab and pertuzumab) and AC-THP (doxorubicin, cyclophosphamide followed by docetaxel/nab-paclitaxel, trastuzumab and pertuzumab) for human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer at a retrospective cohort. Methods: This retrospective study included the patients with HER2+ early-stage breast cancer who received NACT with the regimen TCbHP or AC-THP and then underwent surgery from 2019 to 2022. pCR rate and breast-conserving rate were calculated to evaluate the efficacy of the regimens. Left ventricular ejection fraction (LVEF) from echocardiograms and abnormal electrocardiographs (ECGs) were collected to evaluate the cardiotoxicity of the two regimens. Association between the characteristics of the breast cancer lesions by magnetic resonance imaging (MRI) and the pCR rate were also explored. Results: A total of 159 patients were enrolled, including 48 patients in the AC-THP group and 111 patients in the TCbHP group. The pCR rate of the TCbHP group 64.0% (71/111) was significantly higher than that of for the the AC-THP group 37.5% (18/48) (P=0.002). Estrogen receptor (ER) status (P=0.011, OR: 0.437, 95% CI: 0.231-0.829), progesterone receptor (PR) status (P=0.001, OR: 0.309, 95% CI: 0.157-0.608) and IHC HER2 status (P=0.003, OR: 7.167, 95% CI: 1.970-26.076) were significantly correlated with the pCR rate. LVEF decreased at 6 and 12 months after treatment in the AC-THP group (P=0.024 and 0.040), which only decreased after 6 months of treatment in the TCbHP group (P=0.048). Post-NACT MRI characteristics including mass features (P<0.001) and enhancement type (P<0.001) were significantly associated with pCR rate. Conclusions: Early-stage HER2+ breast cancer treated with the TCbHP regimen has a higher pCR rate than the AC-THP group. The TCbHP regimen appears to have lower cardiotoxicity than the AC-THP regimen in terms of LVEF. Mass features and enhancement type at post-NACT MRI significantly associated with the pCR rate of breast cancer patients.

Ectopic expression of MmSERT, a mouse serotonin transporter gene, regulates salt tolerance and ABA sensitivity in apple and Arabidopsis.

5-hydroxytryptamine (5-HT) is ubiquitously present in animals and plants, playing a vital regulatory role. SERT, a conserved serotonin reuptake transporter in animals, regulates intracellular and extracellular concentrations of 5-HT. Few studies have reported 5-HT transporters in plants. Hence, we cloned MmSERT, a serotonin reuptake transporter, from Mus musculus. Ectopic expression of MmSERT into apple calli, apple roots and Arabidopsis. Because 5-HT plays a momentous role in plant stress tolerance, we used MmSERT transgenic materials for stress treatment. We found that MmSERT transgenic materials, including apple calli, apple roots and Arabidopsis, exhibited a stronger salt tolerance phenotype. The reactive oxygen species (ROS) produced were significantly lower in MmSERT transgenic materials compared with controls under salt stress. Meanwhile, MmSERT induced the expression of SOS1, SOS3, NHX1, LEA5 and LTP1 in response to salt stress. 5-HT is the precursor of melatonin, which regulates plant growth under adversity and effectively scavenges ROS. Detection of MmSERT transgenic apple calli and Arabidopsis revealed higher melatonin levels than controls. Besides, MmSERT decreased the sensitivity of apple calli and Arabidopsis to abscisic acid (ABA). In summary, these results demonstrated that MmSERT plays a vital role in plant stress resistances, which perhaps serves as a reference for the application of transgenic technology to improve crops in the future.

Ectopic expression of MmCYP1A1, a mouse cytochrome P450 gene, positively regulates stress tolerance in apple calli and Arabidopsis.

KEY MESSAGE: Ectopic expression of MmCYP1A1 gene from Mus musculus in apple calli and Arabidopsis increased the levels of melatonin and 6-hydroxymelatonin, and improved their stress resistance. Melatonin occurs widely in organisms, playing a key regulatory role. CYP1A1 is a cytochrome P450 monooxygenase, involved in the melatonin metabolism, and is responsible for the synthesis of 6-hydroxymelatonin from melatonin. Melatonin and 6-hydroxymelatonin have strong antioxidant activities in animals. Here, we cloned MmCYP1A1 from Mus musculus and found that ectopic expression of MmCYP1A1 improved the levels of melatonin and 6-hydroxymelatonin in transgenic apple calli and Arabidopsis. Subsequently, we observed that MmCYP1A1 increased the tolerance of transgenic apple calli and Arabidopsis to osmotic stress simulated by polyethylene glycol 6000 (PEG 6000), as well as resistance of transgenic Arabidopsis to drought stress. Further, the number of lateral roots of MmCYP1A1 transgenic Arabidopsis were enhanced significantly after PEG 6000 treatment. The expression of MmCYP1A1 remarkably reduced malondialdehyde (MDA) content, electrolyte leakage, accumulation of H2O2 and O2- during stress treatment. Moreover, MmCYP1A1 enhanced stress tolerance in apple calli and Arabidopsis by increasing the expression levels of resistance genes. MmCYP1A1 also promoted stomatal closure in transgenic Arabidopsis to reduce leaf water loss during drought. Our results indicate that MmCYP1A1 plays a key role in plant stress tolerance, which may provide a reference for future plant stress tolerance studies.

Influence of neo-adjuvant radiotherapy on the intestinal microbiota of rectal cancer patients.

PURPOSE: Neo-adjuvant radiotherapy (NART) is a widely used pre-surgery radiotherapy for rectal cancer patients. Although NART is effective in reducing tumor burden before surgery, it may cause dysbiosis of intestinal microbiota. The intestinal microbiota shapes tumor inflammatory environment and influences cancer progression. However, how NART remodels the microbiota and how the microbiota affects therapeutic efficacy has been largely elusive. This study aimed to reveal the details of how NART affects the intestinal microbiota in patients with rectal cancer. METHODS: Rectal cancer patients who received NART were recruited into the study, and their healthy family members on the same diet served as controls. Stool samples from five rectal cancer patients (28 in total) and five healthy individuals (16 in total) were collected for intestinal microbiota analysis by 16S rRNA gene amplicon sequencing. Samples from patients were divided into earlier- and later-NART according to the number of NART. RESULTS: NART did not significantly affect the α diversity of intestinal microbiota. However, the abundance of bacterial genera associated with cancer progression tended to decrease in later-NART patients. More importantly, a variety of oral pathogenic bacteria were enriched in the intestine of later-NART patients. NART also affected functional pathways associated with the microbiota in DNA repair, metabolism, and bacterial infection. CONCLUSION: NART significantly altered the microbiota composition and function in rectal cancer patients, and some oral pathogens were found to translocate to the intestine. This is the first report to study the effect of NART on intestinal microbiota in patients with rectal cancer, exploring the importance of intestinal microbiota during the process of NART.

The BTB protein MdBT2 recruits auxin signaling components to regulate adventitious root formation in apple.

Ubiquitination is an important post-translational protein modification. Although BROAD-COMPLEX, TRAMTRACK AND BRIC A BRAC and TRANSCRIPTION ADAPTOR PUTATIVE ZINC FINGER domain protein 2 (BT2) is involved in many biological processes, its role in apple (Malus domestic) root formation remains unclear. Here, we revealed that MdBT2 inhibits adventitious root (AR) formation through interacting with AUXIN RESPONSE FACTOR8 (MdARF8) and INDOLE-3-ACETIC ACID INDUCIBLE3 (MdIAA3). MdBT2 facilitated MdARF8 ubiquitination and degradation through the 26S proteasome pathway and negatively regulated GRETCHEN HAGEN 3.1 (MdGH3.1) and MdGH3.6 expression. MdARF8 regulates AR formation through inducing transcription of MdGH3s (MdGH3.1, MdGH3.2, MdGH3.5, and MdGH3.6). In addition, MdBT2 facilitated MdIAA3 stability and slightly promoted its interaction with MdARF8. MdIAA3 inhibited AR formation by forming heterodimers with MdARF8 as well as other MdARFs (MdARF5, MdARF6, MdARF7, and MdARF19). Our findings reveal that MdBT2 acts as a negative regulator of AR formation in apple.

The MdABI5 transcription factor interacts with the MdNRT1.5/MdNPF7.3 promoter to fine-tune nitrate transport from roots to shoots in apple.

Nitrate is a major nitrogen resource for plant growth and development and acts as both a crucial nutrient and a signaling molecule for plants; hence, understanding nitrate signaling is important for crop production. Abscisic acid (ABA) has been demonstrated to be involved in nitrate signaling, but the underlying mechanism is largely unknown in apple. In this study, we found that exogenous ABA inhibited the transport of nitrate from roots to shoots in apple, and the transcription of the nitrate transporter MdNRT1.5/MdNPF7.3 was noticeably reduced at the transcriptional level by ABA, which inhibited the transport of nitrate from roots to shoots. Then, it was found that the ABA-responsive transcription factor MdABI5 bound directly to the ABRE recognition site of the MdNRT1.5 promoter and suppressed its expression. Overexpression of MdABI5 inhibited ABA-mediated transport of nitrate from roots to shoots. Overall, these results demonstrate that MdABI5 regulates the transport of nitrate from roots to shoots partially by mediating the expression of MdNRT1.5, illuminating the molecular mechanism by which ABA regulates nitrate transport in apple.

Jasmonate induces biosynthesis of anthocyanin and proanthocyanidin in apple by mediating the JAZ1-TRB1-MYB9 complex.

Jasmonate (JA) induces the biosynthesis of anthocyanin and proanthocyanidin. MdMYB9 is essential for modulating the accumulation of both anthocyanin and proanthocyanidin in apple, but the molecular mechanism for induction of anthocyanin and proanthocyanidin biosynthesis by JA is unclear. In this study, we discovered an apple telomere-binding protein (MdTRB1) to be the interacting protein of MdMYB9. A series of biological assays showed that MdTRB1 acted as a positive modulator of anthocyanin and proanthocyanidin accumulation, and is dependent on MdMYB9. MdTRB1 interacted with MdMYB9 and enhanced the activation activity of MdMYB9 to its downstream genes. In addition, we found that the JA signaling repressor MdJAZ1 interacted with MdTRB1 and interfered with the interaction between MdTRB1 and MdMYB9, therefore negatively modulating MdTRB1-promoted biosynthesis of anthocyanin and proanthocyanidin. These results show that the JAZ1-TRB1-MYB9 module dynamically modulates JA-mediated accumulation of anthocyanin and proanthocyanidin. Taken together, our data further expand the functional study of TRB1 and provide insights for further studies of the modulation of anthocyanin and proanthocyanidin biosynthesis by JA.

Low nitrate alleviates iron deficiency by regulating iron homeostasis in apple.

Iron (Fe) is an essential element for plant growth, development and metabolism. Due to its lack of solubility and low bioavailability in soil, Fe levels are usually far below the optimum amount for most plants' growth and development. In apple production, excessive use of nitrogen fertilizer may cause iron chlorosis symptoms in the newly growing leaves, but the regulatory mechanisms underlying this phenomenon are unclear. In this study, low nitrate (NO3- , LN) application alleviated the symptoms of Fe deficiency and promoted lower rhizosphere pH, which was beneficial for root Fe acquisition. At the same time, LN treatment increased citrate and abscisic acid accumulation in roots, which promoted Fe transport from root to shoot and maintained Fe homeostasis. Moreover, qRT-PCR analysis showed that nitrate application caused differential expression of genes related to Fe uptake and transport, as well as transcriptional regulators. In summary, our data reveal that low nitrate alleviated Fe deficiency through multiple pathways, demonstrating a new option for minimizing Fe deficiency by regulating the balance between nutrients.

Automatic model for cervical cancer screening based on convolutional neural network: a retrospective, multicohort, multicenter study.

BACKGROUND: The incidence rates of cervical cancer in developing countries have been steeply increasing while the medical resources for prevention, detection, and treatment are still quite limited. Computer-based deep learning methods can achieve high-accuracy fast cancer screening. Such methods can lead to early diagnosis, effective treatment, and hopefully successful prevention of cervical cancer. In this work, we seek to construct a robust deep convolutional neural network (DCNN) model that can assist pathologists in screening cervical cancer. METHODS: ThinPrep cytologic test (TCT) images diagnosed by pathologists from many collaborating hospitals in different regions were collected. The images were divided into a training dataset (13,775 images), validation dataset (2301 images), and test dataset (408,030 images from 290 scanned copies) for training and effect evaluation of a faster region convolutional neural network (Faster R-CNN) system. RESULTS: The sensitivity and specificity of the proposed cervical cancer screening system was 99.4 and 34.8%, respectively, with an area under the curve (AUC) of 0.67. The model could also distinguish between negative and positive cells. The sensitivity values of the atypical squamous cells of undetermined significance (ASCUS), the low-grade squamous intraepithelial lesion (LSIL), and the high-grade squamous intraepithelial lesions (HSIL) were 89.3, 71.5, and 73.9%, respectively. This system could quickly classify the images and generate a test report in about 3 minutes. Hence, the system can reduce the burden on the pathologists and saves them valuable time to analyze more complex cases. CONCLUSIONS: In our study, a CNN-based TCT cervical-cancer screening model was established through a retrospective study of multicenter TCT images. This model shows improved speed and accuracy for cervical cancer screening, and helps overcome the shortage of medical resources required for cervical cancer screening.

MdABI5 works with its interaction partners to regulate abscisic acid-mediated leaf senescence in apple.

Abscisic acid (ABA) induces chlorophyll degradation and leaf senescence; however, the molecular mechanism remains poorly understood, especially in woody plants. In this study, we found that MdABI5 plays an essential role in the regulation of ABA-triggered leaf senescence in Malus domestica (apple). Through yeast screening, three transcription factors, MdBBX22, MdWRKY40 and MdbZIP44, were found to interact directly with MdABI5 in vitro and in vivo. Physiological and biochemical assays showed that MdBBX22 delayed leaf senescence in two pathways. First, MdBBX22 interacted with MdABI5 to inhibit the transcriptional activity of MdABI5 on the chlorophyll catabolic genes MdNYE1 and MdNYC1, thus negatively regulating chlorophyll degradation and leaf senescence. Second, MdBBX22 interacted with MdHY5 to interfere with the transcriptional activation of MdHY5 on MdABI5, thereby inhibiting the expression of MdABI5, which also contributed to the delay of leaf senescence. MdWRKY40 and MdbZIP44 were identified as positive regulators of leaf senescence. They accelerated MdABI5-promoted leaf senescence through the same regulatory pathways, i.e., interacting with MdABI5 to enhance the transcriptional activity of MdABI5 on MdNYE1 and MdNYC1. Taken together, our results suggest that MdABI5 works with its positive or negative interaction partners to regulate ABA-mediated leaf senescence in apple, in which it acts as a core regulator. The antagonistic regulation pathways ensure that plants respond to external stresses flexibly and efficiently. Our results provide a concept for further study on the regulation mechanisms of leaf senescence.

The BTB-TAZ protein MdBT2 negatively regulates the drought stress response by interacting with the transcription factor MdNAC143 in apple.

Drought stress is a severe source of abiotic stress that can affect apple yield and quality, yet the underlying molecular mechanism of the drought stress response and the role of MdBT2 in the process remain unclear. Here, we find that MdBT2 negatively regulates the drought stress response. Both in vivo and in vitro assays indicated that MdBT2 interacted physically with and ubiquitinated MdNAC143, a member of the NAC TF family that is a positive regulator under drought stress. In addition, MdBT2 promotes the degradation of MdNAC143 via the 26S proteasome system. A series of transgenic assays in apple calli and Arabidopsis verify that MdBT2 confers susceptibility to drought stress at least in part by the regulation of MdNAC143. Overall, our findings provide new insight into the mechanism of MdBT2, which functions antagonistically to MdNAC143 in regulating drought stress by regulating the potential downstream target protein MdNAC143 for proteasomal degradation in apple.

Genome-wide identification and expression analysis of the Dof gene family under drought stress in tea (Camellia sinensis).

BACKGROUND: DNA-binding one zinc finger (Dof) proteins are plant-specific transcription factors important for seed development, hormone regulation, and defense against abiotic stress. Although drought stress is a key determinant of plant physiology and metabolic homeostasis, the role of Dof genes in different degrees of PEG6000-induced drought stress has received little attention. METHODS: Tea plants (Camellia sinensis) were exposed to mild, moderate and severe drought stress. The Tea Genome and Plant TFDB databases were used to identify Dof gene family members in the tea plant. Clustal W2.1, MEGA6.0, ScanProsite, SMART, ExPASy, GSDS, MEME and STRING were used to build a phylogenetic tree, predict the molecular masses and isoelectric points of the Dof proteins, and construct a predicted protein-protein interaction network between the CsDof TFs and proteins in the A. thaliana database. The expression patterns of Dof genes in different tissues were analyzed, and qRT-PCR was used to measure the expression of Dof genes under different degrees of drought stress in tea. RESULTS: We identified 16 Dof genes in tea (C. sinensis cv. Huangjinya) using whole-genome analysis. Through comparative analysis of tea and Arabidopsis thaliana, we divided the Dof genes into four families (A, B, C, and D). We identified 15 motifs in the amino acid sequences of the CsDof proteins. Gene sequences and motif structures were highly conserved among families, especially in the B1 and C2 subfamilies. The protein-protein interaction network indicated that multiple CsDof proteins may be involved in the response to drought stress. Real-time PCR was used to examine the tissue-specific expression patterns of the CsDof genes and to measure their responses to different levels of PEG6000-induced drought stress in mature leaves. Most CsDof genes responded to drought stress. These results provide information on the Dof gene family in tea, offer new insights into the function of CsDof genes in a perennial species, and lay the foundation for further analysis of their functions.

Phosphate regulates malate/citrate-mediated iron uptake and transport in apple.

The accumulation of iron (Fe) in the apical meristem is considered as a critical factor involved in limiting the elongation of roots under low phosphate (Pi) conditions. Furthermore, the antagonism between Fe and Pi largely affects the effective utilization of Fe. Although the lack of Pi serves to increase the effectiveness of Fe in rice under both Fe-sufficient and Fe-deficient conditions, the underlying physiological mechanism governing this phenomenon is still unclear. In this study, we found that low Pi alleviated the Fe-deficiency phenotype in apples. Additionally, low Pi treatments increased ferric-chelated reductase (FCR) activity in the rhizosphere, promoted proton exocytosis, and enhanced the Fe concentration in both the roots and shoots. In contrast, high Pi treatments inhibited this process. Under conditions of low Pi, malate and citrate exudation from apple roots occurred under both Fe-sufficient and Fe-deficient conditions. In addition, treatment with 0.5 mM malate and citrate effectively alleviated the Fe and Pi deficiencies. Taken together, these data support the conclusion that a low Pi supply promotes organic acids exudation and enhances Fe absorption during Fe deficiency in apples.

[Impact of Biochar on Soil Bulk Density and Aggregates of Lou Soil].

The effect of biochar on the bulk density and aggregate stability of Lou soil was evaluated and compared after biochar was applied for 2 years and 5 years through a field-positioning experiment. Five biochar amounts were applied in this study, as follows:0 t·hm-2 (B0), 20 t·hm-2 (B20), 40 t·hm-2 (B40), 60 t·hm-2 (B60), and 80 t·hm-2 (B80). The biochar was produced by pyrolysis of stems and branches from fruit trees at the temperature of 450℃ with limited oxygen apply. At the beginning of the study, biochar was mixed thoroughly with the surface soil (0-20 cm). After 5 years, the soil bulk density and aggregate stability of 0-30 cm soil layers (0-10, 10-20, and 20-30 cm) were measured and compared with the results obtained after 2 years with the purpose of observing the long-term and persist effects of biochar application. The results showed that:① compared with the results after 2 years of application, the effect of biochar on the aggregates at depths of 0-10 cm and 10-20 cm after 5 years were less distinct, and the effect on soil aggregates at depths of 20-30 cm was significantly enhanced; ② compared with the 2 year application, the aggregate stability and the content of the>0.25 mm aggregate size fraction were significantly increased at 0-10 cm depths after 5 years of biochar application at a rate of 40 t·hm-2, while bulk density was significantly decreased; at 10-20 cm and 20-30 cm soil depths, the stability of aggregates and the content of the>0.25 mm aggregate size fraction was significantly increased, while the bulk density was significantly decreased after 5 years of biochar application at a rate of 60-80 t·hm-2;③ when the biochar application rate was 60 t·hm-2, the increase in soil organic carbon was the highest after 5 years. After biochar was applied for 5 years, its effect was more significant lower in the soil profile; the soil bulk density was significantly reduced, and aggregate stability and the content of>0.25 mm aggregates were significantly increased at depths of 20-30 cm. Based on a comprehensive evaluation of the improvement effects and economic benefits, the most suitable biochar application rate was found to be 40-60 t·hm-2. It was further concluded that the effect of biochar on soil aggregates was gradual and sustainable.

DeepHLApan: A Deep Learning Approach for Neoantigen Prediction Considering Both HLA-Peptide Binding and Immunogenicity.

Neoantigens play important roles in cancer immunotherapy. Current methods used for neoantigen prediction focus on the binding between human leukocyte antigens (HLAs) and peptides, which is insufficient for high-confidence neoantigen prediction. In this study, we apply deep learning techniques to predict neoantigens considering both the possibility of HLA-peptide binding (binding model) and the potential immunogenicity (immunogenicity model) of the peptide-HLA complex (pHLA). The binding model achieves comparable performance with other well-acknowledged tools on the latest Immune Epitope Database (IEDB) benchmark datasets and an independent mass spectrometry (MS) dataset. The immunogenicity model could significantly improve the prediction precision of neoantigens. The further application of our method to the mutations with pre-existing T-cell responses indicating its feasibility in clinical application. DeepHLApan is freely available at https://github.com/jiujiezz/deephlapan and http://biopharm.zju.edu.cn/deephlapan.

MdMYB58 Modulates Fe Homeostasis by Directly Binding to the MdMATE43 Promoter in Plants.

Nutrient element deprivation, such as iron (Fe) deficiency stress, is a major factor limiting plant survival and proliferation in marginal soils. To cope with a low Fe environment, plants have evolved elaborate mechanisms underlying Fe homeostasis via intricate transcriptional and post-transcriptional regulation. Here, we characterized the Fe deficiency-inducible MYB transcription factor MdMYB58 in apple plants. Overexpressing MdMYB58 resulted in the accumulation of Fe in the root of transgenic Arabidopsis and apple calli when they were exposed to low Fe available conditions. Further investigation revealed that MdMYB58 bound to the promoter of MdMATE43, and its homolog FRD3 in Arabidopsis. Transient expression and stable transgenic assays in apple calli indicated that MdMYB58 transcriptionally repressed MdMATE43 mRNA, as well as FRD3 in Arabidopsis. Interestingly, AtMYB58, the homolog of MdMYB58, possessed higher binding activities to MdMATE43 and FRD3, which suggests a potentially conserved feature of MYB58 binding to MATE transporters in plants. Additionally, MYB-MATE-mediated regulation of Fe homeostasis may be related to the PYE-related Fe deficiency regulatory network via MdSAT1, a member of the IVa subfamily of bHLH transcription factors. Co-overexpression of MdSAT1 competitively weakened MdMYB58-overexpression induced repression of MdMATE43 transcript abundancy by protein-protein interaction. Taken together, the newly identified MYB-bHLH transcription factor expands our understanding of multilevel molecular mechanisms that plants use to coordinate Fe demand with Fe uptake, transport, and tissue partitioning under low Fe conditions.

Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity.

The immune checkpoint molecules are emerged in the evolution to protect the host from self-attacks by activated T cells. However, cancer cells, as a strategy to survive and expand, can hijack these molecules and mechanisms to suppress T cell-mediated immune responses. Therefore, an idea of blocking the checkpoint molecules to enhance the anti-tumor activities of the host immune system has been developed and applied to the cancer therapy after discovery of the inhibitory T cell co-receptor, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and further enhanced on the identification of PD-1 and its ligands. Since 2010, several checkpoint inhibitors have been approved by FDA and many more are in clinical trials. In the treatment of advanced cancers, these inhibitors significantly increased response rates and survival benefits. However, accompanied with the striking results, immune-related adverse events (irAEs) that broadly occurred in many organs were observed and reported, some of which were fatal. Herein, we first review the recent progressions in the research of the immune checkpoint molecules and the application of their blocking antibodies in cancer treatment, and then discuss the cardiac toxicity induced by the therapy and the strategy to monitor, manage this adverse event when it occurs.