Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration.

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Predicting chronological age of 14 or 18 in adolescents: integrating dental assessments with machine learning.

AIM: Age estimation plays a critical role in personal identification, especially when determining compliance with the age of consent for adolescents. The age of consent refers to the minimum age at which an individual is legally considered capable of providing informed consent for sexual activities. The purpose of this study is to determine whether adolescents meet the age of 14 or 18 by using dental development combined with machine learning. METHODS: This study combines dental assessment and machine learning techniques to predict whether adolescents have reached the consent age of 14 or 18. Factors such as the staging of the third molar, the third molar index, and the visibility of the periodontal ligament of the second molar are evaluated. RESULTS: Differences in performance metrics indicate that the posterior probabilities achieved by machine learning exceed 93% for the age of 14 and slightly lower for the age of 18. CONCLUSION: This study provides valuable insights for forensic identification for adolescents in personal identification, emphasizing the potential to improve the accuracy of age determination within this population by combining traditional methods with machine learning. It underscores the importance of protecting and respecting the dignity of all individuals involved.

3D-printed bredigite scaffolds with ordered arrangement structures promote bone regeneration by inducing macrophage polarization in onlay grafts.

Bone tissue engineering scaffolds may provide a potential strategy for onlay bone grafts for oral implants. For determining the fate of scaffold biomaterials and osteogenesis effects, the host immune response is crucial. In the present study, bredigite (BRT) bioceramic scaffolds with an ordered arrangement structure (BRT-O) and a random morphology (BRT-R) were fabricated. The physicochemical properties of scaffolds were first characterized by scanning electron microscopy, mechanical test and micro-Fourier transform infrared spectroscopy. In addition, their osteogenic and immunomodulatory properties in an onlay grafting model were investigated. In vitro, the BRT-O scaffolds facilitated the macrophage polarization towards a pro-regenerative M2 phenotype, which subsequently facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. In vivo, an onlay grafting model was successfully established in the cranium of rabbits. In addition, the BRT-O scaffolds grafted on rabbit cranium promoted bone regeneration and CD68 + CD206 + M2 macrophage polarization. In conclusion, the 3D-printed BRT-O scaffold presents as a promising scaffold biomaterial for onlay grafts by regulating the local immune microenvironment.

Pancoronary plaque characteristics in STEMI patients with rapid plaque progression: An optical coherence tomography study.

BACKGROUND: Non-culprit plaque progression is associated with recurrent cardiac ischemic events and worse clinical outcomes. Given that atherosclerosis is a systemic disease, the pancoronary characteristics of patients with rapid plaque progression are unknown. This study aims to identify pancoronary plaque features in patients with ST-segment elevation myocardial infarction (STEMI) with and without rapid plaque progression, focused on the patient level. METHODS AND RESULTS: From January 2017 to July 2019, 291 patients underwent 3-vessel optical coherence tomography imaging at the time of the primary procedure and a follow-up angiography interval of 12 months. The final analysis included 237 patients. Overall, 308 non-culprit lesions were found in 78 STEMI patients with rapid plaque progression, and 465 non-culprit plaques were found in 159 STEMI patients without rapid plaque progression. These patients had a higher pancoronary vulnerability (CLIMA-defined high-risk plaque: 47.4% vs. 33.3%; non-culprit plaque rupture: 25.6% vs. 14.5%) and a significantly higher prevalence of other vulnerable plaque characteristics (i.e., lipid-rich plaque, cholesterol crystal, microchannels, calcification, spotty calcification, and thrombus) at baseline versus those without rapid plaque progression. Lesions with rapid progression were highly distributed at the LAD, tending to be near the bifurcation. In multivariate analysis, age ≥ 65 years was an independent predictor of subsequent rapid lesion progression at the patient level, whereas microchannel, spotty calcification, and cholesterol crystal were independent predictors for STEMI patients ≥65 years old. CONCLUSIONS: STEMI patients with subsequent rapid plaque progression had higher pancoronary vulnerability and commonly presented vulnerable plaque morphology. Aging was the only predictor of subsequent rapid plaque progression.

Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer.

Trastuzumab resistance in HER2+ breast cancer (BC) is the major reason leading to poor prognosis of BC patients. Oncogenic gene overexpression or aberrant activation of tyrosine kinase SRC is identified to be the key modulator of trastuzumab response. However, the detailed regulatory mechanisms underlying SRC activation-associated trastuzumab resistance remain poorly understood. In the present study, we discover that SRC-mediated YAP1 tyrosine phosphorylation facilitates its interaction with transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha, TFAP2A), which in turn promotes YAP1/TEAD-TFAP2A (YTT) complex-associated transcriptional outputs, thereby conferring trastuzumab resistance in HER2+ BC. Inhibition of SRC kinase activity or disruption of YTT complex sensitizes cells to trastuzumab treatment in vitro and in vivo. Additionally, we also identify YTT complex co-occupies the regulatory regions of a series of genes related to trastuzumab resistance and directly regulates their transcriptions, including EGFR, HER2, H19 and CTGF. Moreover, YTT-mediated transcriptional regulation is coordinated by SRC kinase activity. Taken together, our study reveals that SRC-mediated YTT complex formation and transcriptions are responsible for multiple mechanisms associated with trastuzumab resistance. Therefore, targeting HER2 signaling in combination with the inhibition of YTT-associated transcriptional outputs could serve as the treatment strategy to overcome trastuzumab resistance caused by SRC activation.

Enhancing lipid peroxidation via radical chain transfer reaction for MRI guided and effective cancer therapy in mice.

Lipid peroxidation (LPO), the process of membrane lipid oxidation, is a potential new form of cell death for cancer treatment. However, the radical chain reaction involved in LPO is comprised of the initiation, propagation (the slowest step), and termination stages, limiting its effectiveness in vivo. To address this limitation, we introduce the radical chain transfer reaction into the LPO process to target the propagation step and overcome the sluggish rate of lipid peroxidation, thereby promoting endogenous lipid peroxidation and enhancing therapeutic outcomes. Firstly, radical chain transfer agent (CTA-1)/Fe nanoparticles (CTA-Fe NPs-1) was synthesized. Notably, CTA-1 convert low activity peroxyl radicals (ROO·) into high activity alkoxyl radicals (RO·), creating the cycle of free radical oxidation and increasing the propagation of lipid peroxidation. Additionally, CTA-1/Fe ions enhance reactive oxygen species (ROS) generation, consume glutathione (GSH), and thereby inactivate GPX-4, promoting the initiation stage and reducing termination of free radical reaction. CTA-Fe NPs-1 induce a higher level of peroxidation of polyunsaturated fatty acids in lipid membranes, leading to highly effective treatment in cancer cells. In addition, CTA-Fe NPs-1 could be enriched in tumors inducing potent tumor inhibition and exhibit activatable T1-MRI contrast of magnetic resonance imaging (MRI). In summary, CTA-Fe NPs-1 can enhance intracellular lipid peroxidation by accelerating initiation, propagation, and inhibiting termination step, promoting the cycle of free radical reaction, resulting in effective anticancer outcomes in tumor-bearing mice.

In vitro characterization of alternative l-threonate and d-erythronate catabolic pathways.

l-threonate is the metabolite of vitamin C, while d-erythronate is the metabolite of N-acetyl-d-glucosamine, the nutritional supplement for joint health. They are widely distributed in the environment and human biofluids. Nevertheless, the catabolisms of l-threonate and d-erythronate are sparsely reported. Here we explored the functional diversity of an acid sugar kinase family (Pfam families PF07005-PF17042), and discovered a novel 2-oxo-tetronate kinase. The conserved genome neighborhood of the 2-oxo-tetronate kinase encodes members of class-II fructose-bisphosphate aldolase family (F_bP_aldolase, PF01116) and a dehydrogenase family (PF03446-PF14833). Instructed by this analysis, we experimentally verified that these enzymes are capable of degrading l-threonate into dihydroxyacetone phosphate (DHAP) in Arthrobacter sp. ZBG10, Clostridium scindens ATCC 35704, and Pseudonocardia dioxanivorans ATCC 55486. Meanwhile, a convergent catabolic pathway for d-erythronate was characterized in P. dioxanivorans ATCC 55486. Moreover, the phylogenetic distribution analysis indicates that the biological range of the identified l-threonate and d-erythronate catabolic pathways appears to extend mostly to members of the Actinomycetota, Cyanobacteriota, Bacillota, Pseudomonadota, and Bacteroidota phyla.

Decarburization of Wire-Arc Additively Manufactured ER70S-6 Steel.

Decarburization is an unwanted carbon-loss phenomenon on the surfaces of a material when they are exposed to oxidizing environments at elevated temperatures. Decarburization of steels after heat treatment has been widely studied and reported. However, up to now, there has not been any systematic study on the decarburization of additively manufactured parts. Wire-arc additive manufacturing (WAAM) is an efficient additive manufacturing process for producing large engineering parts. As the parts produced by WAAM are usually large in size, the use of a vacuum environment to prevent decarburization is not always feasible. Therefore, there is a need to study the decarburization of WAAM-produced parts, especially after the heat treatment processes. This study investigated the decarburization of a WAAM-produced ER70S-6 steel using both the as-printed material and samples heat-treated at different temperatures (800 °C, 850 °C, 900 °C, and 950 °C) for different durations (30 min, 60 min, and 90 min). Furthermore, numerical simulation was carried out using Thermo-Calc computational software to predict the carbon concentration profiles of the steel during the heat treatment processes. Decarburization was found to occur not only in the heat-treated samples but also on the surfaces of the as-printed parts (despite the use of Ar for shielding). The decarburization depth was found to increase with an increase in heat treatment temperature or duration. The part heat-treated at the lowest temperature of 800 °C for merely 30 min was observed to have a large decarburization depth of about 200 µm. For the same heating duration of 30 min, an increase in temperature of 150 °C to 950 °C increased the decarburization depth drastically by 150% to 500 µm. This study serves well to demonstrate the need for further study to control or minimize decarburization for the purpose of ensuring the quality and reliability of additively manufactured engineering components.

New insights into the ambivalent role of YAP/TAZ in human cancers.

Hippo signaling was first identified in Drosophila as a key controller of organ size by regulating cell proliferation and anti-apoptosis. Subsequent studies have shown that this pathway is highly conserved in mammals, and its dysregulation is implicated in multiple events of cancer development and progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) (hereafter YAP/TAZ) are the downstream effectors of the Hippo pathway. YAP/TAZ overexpression or activation is sufficient to induce tumor initiation and progression, as well as recurrence and therapeutic resistance. However, there is growing evidence that YAP/TAZ also exert a tumor-suppressive function in a context-dependent manner. Therefore, caution should be taken when targeting Hippo signaling in clinical trials in the future. In this review article, we will first give an overview of YAP/TAZ and their oncogenic roles in various cancers and then systematically summarize the tumor-suppressive functions of YAP/TAZ in different contexts. Based on these findings, we will further discuss the clinical implications of YAP/TAZ-based tumor targeted therapy and potential future directions.

Porphyromonas gingivalis promotes malignancy and chemo-resistance via GSK3ß-mediated mitochondrial oxidative phosphorylation in human esophageal squamous cell carcinoma.

Our prior studies have confirmed that long-term colonization of Porphyromonas gingivalis (Pg) and overexpression of the inflammatory factor glycogen synthase kinase 3ß (GSK3ß) promote the malignant evolution of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the functional mechanism by which Pg could promote ESCC malignancy and chemo-resistance through GSK3ß-mediated mitochondrial oxidative phosphorylation (mtOXPHOS), and the clinical implications. The effects of Pg and GSK3ß on mtOXPHOS, malignant behaviors and response to paclitaxel and cisplatin treatment of ESCC cells were evaluated by in vitro and in vivo studies. The results showed that Pg induced high expression of the GSK3ß protein in ESCC cells and promoted the progression and chemo-resistance via GSK3ß-mediated mtOXPHOS in human ESCC. Then, Pg infection and the expression of GSK3ß, SIRT1 and MRPS5 in ESCC tissues were detected, and the correlations between each index and postoperative survival of ESCC patients were analysed. The results showed that Pg-positive ESCC patients with high-expression of GSK3ß, SIRT1 and MRPS5 have significant short postoperative survival. In conclusion, we demonstrated that the effective removal of Pg and inhibition of its promotion of GSK3ß-mediated mtOXPHOS may provide a new strategy for ESCC treatment and new insights into the aetiology of ESCC.

Prediction and validation of monoclonal antibodies separation in aqueous two-phase system using molecular dynamic simulation.

In order to predict how mAbs partition in 20% ethylene oxide/80% propylene oxide (v/v) random copolymer (EO20PO80)/water aqueous two-phase system (ATPS), a molecular dynamic simulation model was developed using Gromacs and then validated by experiments. The ATPS was applied with seven kinds of salt, including buffer salt and strong dissociation salt that were commonly employed in the purification of protein. Na2SO4 was shown to have the best effects on lowering EO20PO80 content in the aqueous phase and enhancing recovery. The content of EO20PO80 in the sample solution was decreased to 0.62%±0.25% and the recovery of rituximab increased to 97.88%±0.95% by adding 300 mM Na2SO4 into back extraction ATPS. The viability determined by ELISA was 95.57% at the same time. A strategy for constructing a prediction model for the distribution of mAbs in ATPS was proposed in consideration of this finding. Partition of trastuzumab in ATPS was predicted by the model created using this method and the prediction result was further validated by experiments. The recovery of trastuzumab reached 95.63%±2.86% under the ideal extraction conditions suggested by the prediction model.

The oncogenic roles and clinical implications of YAP/TAZ in breast cancer.

Breast cancer (BC) is the most commonly diagnosed form of cancer and a leading cause of cancer-related deaths among women worldwide. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are homologous transcriptional coactivators and downstream effectors of Hippo signalling. YAP/TAZ activation has been revealed to play essential roles in multiple events of BC development, including tumour initiation, progression, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of YAP/TAZ-mediated oncogenesis in BC, and then systematically summarise the oncogenic roles of YAP/TAZ in various BC subtypes, BC stem cells (BCSCs) and tumour microenvironments (TMEs). Based on these findings, we will further discuss the clinical implications of YAP/TAZ-based targeted therapies in BC and the potential future direction.

Tyrosine kinase SRC-induced YAP1-KLF5 module regulates cancer stemness and metastasis in triple-negative breast cancer.

SRC is the first identified oncogene, and its aberrant activation has been implicated as a driving event in tumor initiation and progression. However, its role in cancer stemness regulation and the underlying regulatory mechanism are still elusive. Here, we identified a YAP1 tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module, as the key downstream mediator of SRC kinase regulating cancer stemness and metastasis in triple-negative breast cancer (TNBC). SRC was overexpressed in TNBC patient tissues and its expression level was highly correlated with the tumor malignancy. SRC activation induced, while inhibition of SRC kinase reduced the cancer stemness, tumor cell growth and metastasis in vitro and in vivo. Transcriptomic and proteomic analysis revealed that SRC-mediated YAP1 tyrosine phosphorylation induced its interaction with Kruppel-like factor 5 (KLF5) to form a YAP1/TEAD-KLF5 complex in TNBC cells. YAP1-KLF5 association further promoted TEAD-mediated transcriptional program independently of canonical Hippo kinases, which eventually gave rise to the enhanced cancer stemness and metastasis. Disruption of YAP1-KLF5 module in TNBC cells dramatically attenuated the SRC-induced cancer stemness and metastasis in vitro and in vivo. Accordingly, co-upregulations of SRC and YAP1-KLF5 module in TNBC tissues were significantly positively correlated with the tumor malignance. Altogether, our work presents a novel tyrosine phosphorylation-dependent YAP1-KLF5 oncogenic module governing SRC-induced cancer stemness and metastasis in TNBC. Therefore, targeting YAP1/KLF5-mediated transcription may provide a promising strategy for TNBC treatment with SRC aberrantly activation.

Three-dimensional assessment of tongue cancer prognosis by preoperative MRI.

PURPOSE: To obtain the relative volume by measuring the tongue volume and the lesion volume, and further explore its relationship with the prognosis of patients, hoping to supplement the TNM staging with a new index. METHODS: ITK-SANP software was used to outline the patients' MRI. After MRI reconstruction and measurement, slicer software was used to estimate tumor volume. RESULTS: A total of 64 patients with tongue cancer who met the inclusion criteria were included in the study. The estimated tumor volume after MRI reconstruction revealed a significant and robust correlation with tumor stage (p < 0.05, Rs = 0.6207) and a substantial and medium correlation with early lymph node metastasis (p < 0.05, Rs = 0.4873). CONCLUSIONS: We classified tongue cancer into three grades based on tumor volume (Stage I, tumors smaller than 1500 mm³; Stage II, tumors 1500-9000 mm³; and Stage III, tumors larger than 9000 mm³), and such grading could be used as a reference for tumor staging, lymph node metastasis, and patient prognosis to a certain extent.

SRC kinase-mediated signaling pathways and targeted therapies in breast cancer.

Breast cancer (BC) has been ranked the most common malignant tumor throughout the world and is also a leading cause of cancer-related deaths among women. SRC family kinases (SFKs) belong to the non-receptor tyrosine kinase (nRTK) family, which has eleven members sharing similar structure and function. Among them, SRC is the first identified proto-oncogene in mammalian cells. Oncogenic overexpression or activation of SRC has been revealed to play essential roles in multiple events of BC progression, including tumor initiation, growth, metastasis, drug resistance and stemness regulations. In this review, we will first give an overview of SRC kinase and SRC-relevant functions in various subtypes of BC and then systematically summarize SRC-mediated signaling transductions, with particular emphasis on SRC-mediated substrate phosphorylation in BC. Furthermore, we will discuss the progress of SRC-based targeted therapies in BC and the potential future direction.

Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.

Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.

N-terminal Domain of Amyloid-ß Impacts Fibrillation and Neurotoxicity.

Alzheimer's disease is characterized by the presence of distinct amyloid-ß peptide (Aß) assemblies with diverse sizes, shapes, and toxicity. However, the primary determinants of Aß aggregation and neurotoxicity remain unknown. Here, the N-terminal amino acid residues of Aß42 that distinguished between humans and rats were substituted. The effects of these modifications on the ability of Aß to aggregate and its neurotoxicity were investigated using biochemical, biophysical, and cellular techniques. The Aß-derived diffusible ligand, protofibrils, and fibrils formed by the N-terminal mutational peptides, including Aß42(R5G), Aß42(Y10F), and rat Aß42, were indistinguishable by conventional techniques such as size-exclusion chromatography, negative-staining transmission electron microscopy and silver staining, whereas the amyloid fibrillation detected by thioflavin T assay was greatly inhibited in vitro. Using circular dichroism spectroscopy, we discovered that both Aß42 and Aß42(Y10F) generated protofibrils and fibrils with a high proportion of parallel ß-sheet structures. Furthermore, protofibrils formed by other mutant Aß peptides and N-terminally shortened peptides were incapable of inducing neuronal death, with the exception of Aß42 and Aß42(Y10F). Our findings indicate that the N-terminus of Aß is important for its fibrillation and neurotoxicity.

Unveiling the Noncanonical Autophagy-Independent Role of ATG7 and ATG9B in Head and Neck Squamous Cell Carcinoma (HNSCC).

The role of autophagy in cancer remains elusive, and nontargeted autophagy inhibitors have limited therapeutic effects in HNSCC. Here, we systematically analyzed the correlation of autophagy-related genes in HNSCC through TCGA and single-cell sequencing data (GSE103322). ATG9B and ATG7 were found to have noncanonical autophagy-independent functions in HNSCC. Specifically, ATG9B was a protective factor in HNSCC patients through downregulating cancer cell EMT, and ATG7 was correlated with the immunosuppressive environment in HNSCC. Mechanistically, single-cell analysis revealed that ATG9B increased the epithelial phenotype of cancer cells but did not influence EMT signaling pathways. ATG7 was strongly correlated with elevated immunosuppressive checkpoints like PD-1, PD-L1, and CTLA4 in HNSCC. Further single-cell analysis and multiple immunofluorescence colocalization analyses indicated that ATG7 contributed to the high expression of PD-L1 in myeloid cells but not cancer cells. Collectively, our results revealed noncanonical autophagy-independent functions of autophagy-related genes. These results increase understanding of the intricacies of autophagy and may contribute to precision treatment using autophagy-targeted therapies.