Surgical gestures to evaluate apical dissection of robot-assisted radical prostatectomy.

Previously, our group established a surgical gesture classification system that deconstructs robotic tissue dissection into basic surgical maneuvers. Here, we evaluate gestures by correlating the metric with surgeon experience and technical skill assessment scores in the apical dissection (AD) of robotic-assisted radical prostatectomy (RARP). Additionally, we explore the association between AD performance and early continence recovery following RARP. 78 AD surgical videos from 2016 to 2018 across two international institutions were included. Surgeons were grouped by median robotic caseload (range 80-5,800 cases): less experienced group (< 475 cases) and more experienced (≥ 475 cases). Videos were decoded with gestures and assessed using Dissection Assessment for Robotic Technique (DART). Statistical findings revealed more experienced surgeons (n = 10) used greater proportions of cold cut (p = 0.008) and smaller proportions of peel/push, spread, and two-hand spread (p < 0.05) than less experienced surgeons (n = 10). Correlations between gestures and technical skills assessments ranged from - 0.397 to 0.316 (p < 0.05). Surgeons utilizing more retraction gestures had lower total DART scores (p < 0.01), suggesting less dissection proficiency. Those who used more gestures and spent more time per gesture had lower efficiency scores (p < 0.01). More coagulation and hook gestures were found in cases of patients with continence recovery compared to those with ongoing incontinence (p < 0.04). Gestures performed during AD vary based on surgeon experience level and patient continence recovery duration. Significant correlations were demonstrated between gestures and dissection technical skills. Gestures can serve as a novel method to objectively evaluate dissection performance and anticipate outcomes.

Capturing relationships between suturing sub-skills to improve automatic suturing assessment.

Suturing skill scores have demonstrated strong predictive capabilities for patient functional recovery. The suturing can be broken down into several substep components, including needle repositioning, needle entry angle, etc. Artificial intelligence (AI) systems have been explored to automate suturing skill scoring. Traditional approaches to skill assessment typically focus on evaluating individual sub-skills required for particular substeps in isolation. However, surgical procedures require the integration and coordination of multiple sub-skills to achieve successful outcomes. Significant associations among the technical sub-skill have been established by existing studies. In this paper, we propose a framework for joint skill assessment that takes into account the interconnected nature of sub-skills required in surgery. The prior known relationships among sub-skills are firstly identified. Our proposed AI system is then empowered by the prior known relationships to perform the suturing skill scoring for each sub-skill domain simultaneously. Our approach can effectively improve skill assessment performance through the prior known relationships among sub-skills. Through the proposed approach to joint skill assessment, we aspire to enhance the evaluation of surgical proficiency and ultimately improve patient outcomes in surgery.

Artificial Intelligence-Based Video Feedback to Improve Novice Performance on Robotic Suturing Skills: A Pilot Study.

Introduction: Automated skills assessment can provide surgical trainees with objective, personalized feedback during training. Here, we measure the efficacy of artificial intelligence (AI)-based feedback on a robotic suturing task. Materials and Methods: Forty-two participants with no robotic surgical experience were randomized to a control or feedback group and video-recorded while completing two rounds (R1 and R2) of suturing tasks on a da Vinci surgical robot. Participants were assessed on needle handling and needle driving, and feedback was provided via a visual interface after R1. For feedback group, participants were informed of their AI-based skill assessment and presented with specific video clips from R1. For control group, participants were presented with randomly selected video clips from R1 as a placebo. Participants from each group were further labeled as underperformers or innate-performers based on a median split of their technical skill scores from R1. Results: Demographic features were similar between the control (n = 20) and feedback group (n = 22) (p > 0.05). Observing the improvement from R1 to R2, the feedback group had a significantly larger improvement in needle handling score (0.30 vs -0.02, p = 0.018) when compared with the control group, although the improvement of needle driving score was not significant when compared with the control group (0.17 vs -0.40, p = 0.074). All innate-performers exhibited similar improvements across rounds, regardless of feedback (p > 0.05). In contrast, underperformers in the feedback group improved more than the control group in needle handling (p = 0.02). Conclusion: AI-based feedback facilitates surgical trainees' acquisition of robotic technical skills, especially underperformers. Future research will extend AI-based feedback to additional suturing skills, surgical tasks, and experience groups.

Evolution of structural rearrangements in prostate cancer intracranial metastases.

Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of prostate cancer intracranial metastases would improve our understanding of their pathogenesis and the search for new treatment strategies. We evaluated the clinical and molecular characteristics of 36 patients with metastatic prostate cancer to either the dura or brain parenchyma. We performed whole genome sequencing (WGS) of 10 intracranial prostate cancer metastases, as well as WGS of primary prostate tumors from men who later developed metastatic disease (n = 6) and nonbrain prostate cancer metastases (n = 36). This first whole genome sequencing study of prostate intracranial metastases led to several new insights. First, there was a higher diversity of complex structural alterations in prostate cancer intracranial metastases compared to primary tumor tissues. Chromothripsis and chromoplexy events seemed to dominate, yet there were few enrichments of specific categories of structural variants compared with non-brain metastases. Second, aberrations involving the AR gene, including AR enhancer gain were observed in 7/10 (70%) of intracranial metastases, as well as recurrent loss of function aberrations involving TP53 in 8/10 (80%), RB1 in 2/10 (20%), BRCA2 in 2/10 (20%), and activation of the PI3K/AKT/PTEN pathway in 8/10 (80%). These alterations were frequently present in tumor tissues from other sites of disease obtained concurrently or sequentially from the same individuals. Third, clonality analysis points to genomic factors and evolutionary bottlenecks that contribute to metastatic spread in patients with prostate cancer. These results describe the aggressive molecular features underlying intracranial metastasis that may inform future diagnostic and treatment approaches.

Tff2 defines transit-amplifying pancreatic acinar progenitors that lack regenerative potential and are protective against Kras-driven carcinogenesis.

While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreERT2-targeted cells defines a transit-amplifying progenitor (TAP) population that contributes to normal homeostasis. Following acute and chronic injury, Tff2+ cells, distinct from FPs, undergo depopulation but are eventually replenished. At baseline, oncogenic KrasG12D-targeted Tff2+ cells are resistant to PDAC initiation. However, KrasG12D activation in Tff2+ cells leads to survival and clonal expansion following pancreatitis and a cancer stem/progenitor cell-like state. Selective ablation of Tff2+ cells prior to KrasG12D activation in Mist1+ acinar or Dclk1+ FP cells results in enhanced tumorigenesis, which can be partially rescued by adenoviral Tff2 treatment. Together, Tff2 defines a pancreatic TAP population that protects against Kras-driven carcinogenesis.

Development of a Classification System for Live Surgical Feedback.

Importance: Live feedback in the operating room is essential in surgical training. Despite the role this feedback plays in developing surgical skills, an accepted methodology to characterize the salient features of feedback has not been defined. Objective: To quantify the intraoperative feedback provided to trainees during live surgical cases and propose a standardized deconstruction for feedback. Design, Setting, and Participants: In this qualitative study using a mixed methods analysis, surgeons at a single academic tertiary care hospital were audio and video recorded in the operating room from April to October 2022. Urological residents, fellows, and faculty attending surgeons involved in robotic teaching cases during which trainees had active control of the robotic console for at least some portion of a surgery were eligible to voluntarily participate. Feedback was time stamped and transcribed verbatim. An iterative coding process was performed using recordings and transcript data until recurring themes emerged. Exposure: Feedback in audiovisual recorded surgery. Main Outcomes and Measures: The primary outcomes were the reliability and generalizability of a feedback classification system in characterizing surgical feedback. Secondary outcomes included assessing the utility of our system. Results: In 29 surgical procedures that were recorded and analyzed, 4 attending surgeons, 6 minimally invasive surgery fellows, and 5 residents (postgraduate years, 3-5) were involved. For the reliability of the system, 3 trained raters achieved moderate to substantial interrater reliability in coding cases using 5 types of triggers, 6 types of feedback, and 9 types of responses (prevalence-adjusted and bias-adjusted κ range: a 0.56 [95% CI, 0.45-0.68] minimum for triggers to a 0.99 [95% CI, 0.97-1.00] maximum for feedback and responses). For the generalizability of the system, 6 types of surgical procedures and 3711 instances of feedback were analyzed and coded with types of triggers, feedback, and responses. Significant differences in triggers, feedback, and responses reflected surgeon experience level and surgical task being performed. For example, as a response, attending surgeons took over for safety concerns more often for fellows than residents (prevalence rate ratio [RR], 3.97 [95% CI, 3.12-4.82]; P = .002), and suturing involved more errors that triggered feedback than dissection (RR, 1.65 [95% CI, 1.03-3.33]; P = .007). For the utility of the system, different combinations of trainer feedback had associations with rates of different trainee responses. For example, technical feedback with a visual component was associated with an increased rate of trainee behavioral change or verbal acknowledgment responses (RR, 1.11 [95% CI, 1.03-1.20]; P = .02). Conclusions and Relevance: These findings suggest that identifying different types of triggers, feedback, and responses may be a feasible and reliable method for classifying surgical feedback across several robotic procedures. Outcomes suggest that a system that can be generalized across surgical specialties and for trainees of different experience levels may help galvanize novel surgical education strategies.

A Multi-institution Study on the Association of Virtual Reality Skills with Continence Recovery after Robot-assisted Radical Prostatectomy.

BACKGROUND: Virtual reality (VR) simulators are increasingly being used for surgical skills training. It is unclear what skills are best improved via VR, translate to live surgical skills, and influence patient outcomes. OBJECTIVE: To assess surgeons in VR and live surgery using a suturing assessment tool and evaluate the association between technical skills and a clinical outcome. DESIGN, SETTING, AND PARTICIPANTS: This prospective five-center study enrolled participants who completed VR suturing exercises and provided live surgical video. Graders provided skill assessments using the validated End-To-End Assessment of Suturing Expertise (EASE) suturing evaluation tool. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A hierarchical Poisson model was used to compare skill scores among cohorts and evaluate the association of scores with clinical outcomes. Spearman's method was used to assess correlation between VR and live skills. RESULTS AND LIMITATIONS: Ten novices, ten surgeons with intermediate expertise (median 64 cases, interquartile range [IQR] 6-80), and 26 expert surgeons (median 850 cases, IQR 375-3000) participated in this study. Intermediate and expert surgeons were significantly more likely to have ideal scores in comparison to novices for the subskills needle hold angle, wrist rotation, and wrist rotation needle withdrawal (p < 0.01). For both intermediate and expert surgeons, there was positive correlation between VR and live skills for needle hold angle (p < 0.05). For expert surgeons, there was a positive association between ideal scores for VR needle hold angle and driving smoothness subskills and 3-mo continence recovery (p < 0.05). Limitations include the size of the intermediate surgeon sample and clinical data limited to expert surgeons. CONCLUSIONS: EASE can be used in VR to identify skills to improve for trainee surgeons. Technical skills that influence postoperative outcomes may be assessable in VR. PATIENT SUMMARY: This study provides insights into surgical skills that translate from virtual simulation to live surgery and that have an impact on urinary continence after robot-assisted removal of the prostate. We also highlight the usefulness of virtual reality in surgical education.

PTPN2 Is a Critical Regulator of Ileal Paneth Cell Viability and Function in Mice.

BACKGROUND & AIMS: Loss-of-function variants in the PTPN2 gene are associated with increased risk of inflammatory bowel disease. We recently showed that Ptpn2 is critical for intestinal epithelial cell (IEC) barrier maintenance, IEC-macrophage communication, and modulation of the gut microbiome in mice, restricting expansion of a small intestinal pathobiont associated with inflammatory bowel disease. Here, we aimed to identify how Ptpn2 loss affects ileal IEC subtypes and their function in vivo. METHODS: Constitutive Ptpn2 wild-type, heterozygous, and knockout (KO) mice, as well as mice with inducible deletion of Ptpn2 in IECs, were used in the study. Investigation was performed using imaging techniques, flow cytometry, enteroid culture, and analysis of gene and protein levels of IEC markers. RESULTS: Partial transcriptome analysis showed that expression of Paneth cell-associated antimicrobial peptides Lyz1, Pla2g2a, and Defa6 was down-regulated markedly in Ptpn2-KO mice compared with wild-type and heterozygous. In parallel, Paneth cell numbers were reduced, their endoplasmic reticulum architecture was disrupted, and the endoplasmic reticulum stress protein, C/EBP-homologous protein (CHOP), was increased in Ptpn2-KO mice. Despite reduced Paneth cell number, flow cytometry showed increased expression of the Paneth cell-stimulatory cytokines interleukin 22 and interferon γ+ in CD4+ T cells isolated from Ptpn2-KO ileum. Key findings in constitutive Ptpn2-KO mice were confirmed in epithelium-specific Ptpn2ΔIEC mice, which also showed impaired lysozyme protein levels in Paneth cells compared with Ptpn2fl/fl control mice. CONCLUSIONS: Constitutive Ptpn2 deficiency affects Paneth cell viability and compromises Paneth cell-specific antimicrobial peptide production. The observed effects may contribute to the increased susceptibility to intestinal infection and dysbiosis in these mice.

Retinoic acid signaling during priming licenses intestinal CD103+ CD8 TRM cell differentiation.

CD8 tissue-resident memory T (TRM) cells provide frontline protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.

The 100 Most-Cited Manuscripts in Hearing Implants: A Bibliometrics Analysis.

The aim of the study was to characterise the most frequently cited articles on the topic of hearing implants. A systematic search was carried out using the Thomson Reuters Web of Science Core Collection database. Eligibility criteria restricted the results to primary studies and reviews published from 1970 to 2022 in English dealing primarily with hearing implants. Data including the authors, year of publication, journal, country of origin, number of citations and average number of citations per year were extracted, as well as the impact factors and five-year impact factor of journals publishing the articles. The top 100 papers were published across 23 journals and were cited 23,139 times. The most-cited and influential article describes the first use of the continuous interleaved sampling (CIS) strategy utilised in all modern cochlear implants. More than half of the studies on the list were produced by authors from the United States, and the Ear and Hearing journal had both the greatest number of articles and the greatest number of total citations. To conclude, this research serves as a guide to the most influential articles on the topic of hearing implants, although bibliometric analyses mainly focus on citations. The most-cited article was an influential description of CIS.

Exploring the Use of Artificial Intelligence in the Management of Prostate Cancer.

PURPOSE OF REVIEW: This review aims to explore the current state of research on the use of artificial intelligence (AI) in the management of prostate cancer. We examine the various applications of AI in prostate cancer, including image analysis, prediction of treatment outcomes, and patient stratification. Additionally, the review will evaluate the current limitations and challenges faced in the implementation of AI in prostate cancer management. RECENT FINDINGS: Recent literature has focused particularly on the use of AI in radiomics, pathomics, the evaluation of surgical skills, and patient outcomes. AI has the potential to revolutionize the future of prostate cancer management by improving diagnostic accuracy, treatment planning, and patient outcomes. Studies have shown improved accuracy and efficiency of AI models in the detection and treatment of prostate cancer, but further research is needed to understand its full potential as well as limitations.

Is Artificial Intelligence Replacing Our Radiology Stars? Not Yet!

Artificial intelligence (AI) is here to stay and will change health care as we know it. The availability of big data and the increasing numbers of AI algorithms approved by the US Food and Drug Administration together will help in improving the quality of care for patients and in overcoming human fatigue barriers. In oncology practice, patients and providers rely on the interpretation of radiologists when making clinical decisions; however, there is considerable variability among readers, and in particular for prostate imaging. AI represents an emerging solution to this problem, for which it can provide a much-needed form of standardization. The diagnostic performance of AI alone in comparison to a combination of an AI framework and radiologist assessment for evaluation of prostate imaging has yet to be explored. Here, we compare the performance of radiologists alone versus a combination of radiologists aided by a modern computer-aided diagnosis (CAD) AI system. We show that the radiologist-CAD combination demonstrates superior sensitivity and specificity in comparison to both radiologists alone and AI alone. Our findings demonstrate that a radiologist + AI combination could perform best for detection of prostate cancer lesions. A hybrid technology-human system could leverage the benefits of AI in improving radiologist performance while also reducing physician workload, minimizing burnout, and enhancing the quality of patient care. Patient summary: Our report demonstrates the potential of artificial intelligence (AI) for improving the interpretation of prostate scans. A combination of AI and evaluation by a radiologist has the best performance in determining the severity of prostate cancer. A hybrid system that uses both AI and radiologists could maximize the quality of care for patients while reducing physician workload and burnout.

Incidence of injuries among lacrosse athletes: a systematic review and meta-analysis.

OBJECTIVES: The purpose of this systematic review was to determine the incidence of injuries among lacrosse athletes and the differences in rates of injury by location and gender. METHODS: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were implemented to conduct this systematic review.[1] The following variables were extracted from each of the included articles: location of injury, gender of patient, and incidence of injury among study population. The methodological quality of the included studies was assessed using mixed-methods appraisal tool (MMAT) version 2018.[2] Estimated rates were reported as pooled proportion with 95% CI. Rates of injury were calculated as a rate per 1000 athletic exposures (AEs), defined as an athlete participating in 1 practice or competition in which he or she was exposed to the possibility of athletic injury. RESULTS: This study found that the highest injury rate among lacrosse athletes was to the lower leg/ankle/foot with a rate of 0.66 injuries per 1000 AEs (95% CI, 0.51, 0.82). This injury pattern was also found to be the highest among both male and female lacrosse athletes. No statistical significance was detected when comparing rates of injury across gender, regardless of location. The injury pattern with the lowest rates of injury for female athletes being to the shoulder/clavicle and the neck for male athletes. CONCLUSION: The highest rate of injury among lacrosse athletes was to the lower leg/ankle/foot. As participation in lacrosse continues to rise, there is a greater need for understanding the rate of injury and injury characteristics for physicians and trainers to provide effective care to lacrosse athletes.

Immune related biomarkers for cancer metastasis to the brain.

Brain metastasis accounts for a large number of cancer-related deaths. The host immune system, involved at each step of the metastatic cascade, plays an important role in both the initiation of the brain metastasis and their treatment responses to various modalities, through either local and or systemic effect. However, few reliable immune biomarkers have been identified in predicting the development and the treatment outcome in patients with cancer brain metastasis. Here, we provide a focused perspective of immune related biomarkers for cancer metastasis to the brain and a thorough discussion of the potential utilization of specific biomarkers such as tumor mutation burden (TMB), genetic markers, circulating and tumor-infiltrating immune cells, cytokines, in predicting the brain disease progression and regression after therapeutic intervention. We hope to inspire the field to extend the research and establish practical guidelines for developing and validating immune related biomarkers to provide personalized treatment and improve treatment outcomes in patients with metastatic brain cancers.

Surgical gestures as a method to quantify surgical performance and predict patient outcomes.

How well a surgery is performed impacts a patient's outcomes; however, objective quantification of performance remains an unsolved challenge. Deconstructing a procedure into discrete instrument-tissue "gestures" is a emerging way to understand surgery. To establish this paradigm in a procedure where performance is the most important factor for patient outcomes, we identify 34,323 individual gestures performed in 80 nerve-sparing robot-assisted radical prostatectomies from two international medical centers. Gestures are classified into nine distinct dissection gestures (e.g., hot cut) and four supporting gestures (e.g., retraction). Our primary outcome is to identify factors impacting a patient's 1-year erectile function (EF) recovery after radical prostatectomy. We find that less use of hot cut and more use of peel/push are statistically associated with better chance of 1-year EF recovery. Our results also show interactions between surgeon experience and gesture types-similar gesture selection resulted in different EF recovery rates dependent on surgeon experience. To further validate this framework, two teams independently constructe distinct machine learning models using gesture sequences vs. traditional clinical features to predict 1-year EF. In both models, gesture sequences are able to better predict 1-year EF (Team 1: AUC 0.77, 95% CI 0.73-0.81; Team 2: AUC 0.68, 95% CI 0.66-0.70) than traditional clinical features (Team 1: AUC 0.69, 95% CI 0.65-0.73; Team 2: AUC 0.65, 95% CI 0.62-0.68). Our results suggest that gestures provide a granular method to objectively indicate surgical performance and outcomes. Application of this methodology to other surgeries may lead to discoveries on methods to improve surgery.

Vaccine protection by Cryptococcus neoformans Δsgl1 is mediated by γδ T cells via TLR2 signaling.

We previously reported that administration of Cryptococcus neoformans Δsgl1 mutant vaccine, accumulating sterylglucosides (SGs) and having normal capsule (GXM), protects mice from a subsequent infection even during CD4+ T cells deficiency, a condition commonly associated with cryptococcosis. Here, we studied the immune mechanism that confers host protection during CD4+T deficiency. Mice receiving Δsgl1 vaccine produce IFNγ and IL-17A during CD4+ T (or CD8+ T) deficiency, and protection was lost when either cytokine was neutralized. IFNγ and/or IL-17A are produced by γδ T cells, and mice lacking these cells are no longer protected. Interestingly, ex vivo γδ T cells are highly stimulated in producing IFNγ and/or IL-17A by Δsgl1 vaccine, but this production was significantly decreased when cells were incubated with C. neoformans Δcap59/Δsgl1 mutant, accumulating SGs but lacking GXM. GXM modulates toll-like receptors (TLRs), including TLR2. Importantly, neither Δsgl1 nor Δcap59/Δsgl1 stimulate IFNγ or IL-17A production by ex vivo γδ T cells from TLR2-/- mice. Finally, TLR2-/- animals do not produce IL-17A in response to Δsgl1 vaccine and were no longer protected from WT challenge. Our results suggest that SGs may act as adjuvants for GXM to stimulate γδ T cells in producing IFNγ and IL-17A via TLR2, a mechanism that is still preserved upon CD4+ T deficiency.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors.

The development of combination immunotherapy based on the mediation of regulatory mechanisms of the tumor immune microenvironment (TIME) is promising. However, a deep understanding of tumor immunology must involve the systemic tumor immune environment (STIE) which was merely illustrated previously. Here, we aim to review recent advances in single-cell transcriptomics and spatial transcriptomics for the studies of STIE, TIME, and their interactions, which may reveal heterogeneity in immunotherapy responses as well as the dynamic changes essential for the treatment effect. We review the evidence from preclinical and clinical studies related to TIME, STIE, and their significance on overall survival, through different immunomodulatory pathways, such as metabolic and neuro-immunological pathways. We also evaluate the significance of the STIE, TIME, and their interactions as well as changes after local radiotherapy and systemic immunotherapy or combined immunotherapy. We focus our review on the evidence of lung cancer, hepatocellular carcinoma, and nasopharyngeal carcinoma, aiming to reshape STIE and TIME to enhance immunotherapy efficacy.