Search

Good traditions should be followed! One such tradition is that Nordic Journal of STEM Education publishes a special volume with papers prepared based on presentations at the biennial MNT (STEM) conference. In line with this volume 8 of the journal is dedicated to articles discussing topics that were presented at the MNT conference in Stavanger in March 2023. The conference attracted a record number of high-quality abstract submissions – far more presentations than we possibly could fit into the two-day program. The scientific review committee therefore had to face a tough challenge to select presentations that could get a slot time for an oral presentation. Many good contributions were therefore presented as posters during the two days. The record interest for contributing with presentations at the conference was also accompanied by a record crowd of participants. Thank you to everybody who came to Stavanger for the conference and a very warm thank you to alle the local organizers making the conference a success! When we meet again in two years’ time it is NTNU’s turn to host the conference. We wish them good luck with their preparations, and we are already looking forward to the next MNT conference in 2025! The all-time high participation at the MNT conference tells us that the interest in learning and sharing knowledge on how to conduct good education for our students is growing. It is very enjoyable to see that, and we know that our subjects are key in order to solve many of the challenges that the society is facing. We hope that the papers published in this volume will be inspirational!

Several universities are witnessing an increase in students’ enrolment in mathematics-intensive programmes over the last decades. This increase has come with the price of high failure rates in foundational mathematics courses, which poses challenges to mathematics teaching and learning in higher education. It is therefore inevitable, for some universities, to transform the teaching and learning of mathematics to more student-centred approaches that engage the students mathematically and enhance their success rates. We approach this transformative effort by investigating students’ perception of teaching, feedback, and assessment as a first step in reforming the teaching of a first-year mathematics course at a Norwegian university. The results of both quantitative and qualitative analyses of the data generated using a questionnaire from 107 (80 men) engineering students show that the status quo of teachings offers little support for learning. The teaching is dominated by teacher-led instruction, note-taking, and large pieces of proof which make learning difficult for students during class activities. The results also show that the current structure of the course offers limited formative feedback to students and that the assessment tasks require restructuring to capture students’ time and effort. We discuss the implications of these findings and make some recommendations for improvement.

I denne presentasjonen vil vi rapportere veilederes erfaringer med å bidra i et matematisk modelleringsprosjekt. Prosjektet ble introdusert i begynnelsen av første semester matematikkurs for ingeniørstudenter. Målet med prosjektet er å knytte matematikken til realistiske ingeniørgfag problemstillinger og at studentene skal få en nærmere tilknytning til faglærerne i sitt felt. Vi ønsker også å lære studentene flere matematiske kompetanser, som det er vanskelig å trene i forelesninger og øvingstimer. I prosjektet ble 483 studenter delt i 70 grupper som ble veiledet av 20 faglig ansatte fra alle seksjoner av ingeniøravdelingene. Veilederne rapporterer om at de opplever prosjektoppgaven som et positivt bidrag i matematikkfaget, og at studentene var fornøyd med denne oppgaven. Veilederne rapporterte også at veiledningen var tidkrevende og at gruppedynamikk var en utfordring.

Integrins are a family of heterodimeric cell surface receptors, which are expressed on most cells where they mediate cell-cell and cell-extracellular matrix (ECM) interactions. The alphavbeta6 integrin is epithelial-specific and binds to the ECM proteins fibronectin, vitronectin and tenascin, and also to the latency associated peptide of TGF-beta. Unlike most epithelial integrins, alphavbeta6 is not expressed constitutively by healthy oral epithelia, but is up-regulated during tissue remodelling, including that accompanying wound healing and carcinogenesis. Although, the data at present have been generated principally from in vitro studies, there is increasing evidence to suggest that alphavbeta6 may promote carcinoma progression: alphavbeta6 has been shown to modulate invasion, inhibit apoptosis, regulate protease expression and activate TGF-beta1. This review examines the current literature, and discusses the possible role of alphavbeta6 in wound healing, and in the development and progression of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: This article explores the influence of patient-specific and organisational factors on adherence to program guidelines in an integrated care program targeting older patients. Methods: The integrated care program aimed to offer post-discharge follow-up visits by a municipality nurse and the general practitioner to frail older patients after discharge from hospital. Adherence was measured as 'step 1') successful referral from the hospital and 'step 2') completed post-discharge follow-up visit. We followed a cohort of 1,659 patients who were selected to receive a post-discharge follow-up visit in 2014. We obtained unique data from hospitals, municipalities and from administrative registers. Results: We found substantial lack of adherence in both steps of the program: 69% adherence in step 1 and 54% adherence in step 2. In step 1, adherence was related to hospital, and receiving municipal home care prior to admission. In step 2, level of adherence varied according to municipality, the type of general practitioner and the patient’s gender. Conclusion: We found that adherence was strongly related to organisational factors. Adherence differed significantly at all organisational levels (hospital, municipality, general practice), thus indicating challenges in the vertical integration of care. Gender influenced adherence as the only patient-related factor.

Context: The illicit drug landscape in the United States is dynamic, featuring a risky and erratic drug supply. Drug checking programs (DCP) have been successfully implemented and studied extensively in Canada and Europe but are scarce in the United States. Integrating DCP at harm reduction programs provides an opportunity to engage people at the point-of-care and deliver a combination of harm reduction services, access to healthcare services, and linkages to treatment., Program: The New York State Department of Health (NYSDOH) developed and supports operation of 8 pilot community DCP sites throughout the state. The DCP were trained to utilize Fourier-transform infrared spectroscopy (FTIR) technology to deliver real-time results to participants., Implementation: The NYSDOH community DCP pilot began development in 2022. Partnerships were formed across multiple domains including other DCP, universities, forensic laboratories, syringe service and harm reduction programs, and legal and regulatory offices within the NYSDOH. The first pilot sites began operating in mid-2023 and program expansion is on-going., Evaluation: Evaluation staff were extensively engaged in development and implementation phases. Qualitative evaluation focused on barriers, facilitators, and lessons learned from program staff and technicians. Quantitative evidence was gathered to assess the reach of the DCP and accuracy of results attained by drug checking technicians during their training periods. Drug checking results helped characterize the illicit drug supply., Discussion: Development and implementation of DCP in NYS was facilitated by strong partnerships across sectors including public health and harm reduction. DCP may involve diverse partners who do not regularly collaborate, and health departments are positioned to build relationships and convene partners for program implementation. Evaluation findings highlight the importance of facilitating on-going training and technical assistance to DCP for quality assurance. The initial successes and lessons learned from the NYSDOH DCP demonstrate state public health departments' ability to successfully deploy this innovative harm reduction strategy., Competing Interests: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The effectiveness of fungicides to control foliar fungal crop diseases is being diminished by the increasing spread of resistances to fungicides. One approach that may help to maintain efficacy is remediation of resistant populations by sensitive ones. However, the success of such approaches can be compromised by re-incursion of resistance through aerial spore dispersal; although, knowledge of localized gene flow is lacking. Here, we report on a replicated mark-release-recapture field experiment with several treatments set up to study spore-dispersal-mediated gene flow of a mutated allele that confers demethylase inhibitor resistance in Pyrenophora teres f. teres ( Ptt ). Artificial inoculation of the host, barley ( Hordeum vulgare ), was successful across the 12-ha trial, where the introduced sensitive- and resistant-populations were, respectively, 6- and 13-fold the DNA concentration of the native Ptt population. Subsequent disease pressure remained low which hampered spread of the epidemic to such extent that gene flow was not detected at, or beyond 2.5 m from source points. In the absence of gene flow, plots were assessed for treatment effects; fungicide applied to populations that contained 14.3% of allele mutation increased in frequency to 24.5%, whereas sensitive populations had no change in structure. Untreated controls of native Ptt population remained genetically stable, yet untreated controls that were inoculated with sensitive Ptt had half the resistance frequency of the native population structure. The trial demonstrates the potential for management to remediate fungicide resistant pathogen populations, where localized gene flow is minimal; to safeguard chemical crop protection into the future.

Purpose: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC., Experimental Design: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort., Results: A total of 985 subjects (median follow-up 5.03 years, range: 4.73-5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery + adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR = 0.32; 95% confidence interval (CI), 0.16-0.65; P = 0.002], but not in the low-risk group (HR = 0.4; 95% CI, 0.14-1.24; P = 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI = 0.17-0.67, P = 0.002, and in the low-risk group HR was 0.5, 95% CI = 0.1-2.38, P = 0.384. The concordance index was 0.73., Conclusions: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: High numbers of tumor-infiltrating lymphocytes (TIL) are linked to better survival in patients with cancer. Tissue-resident memory T cells (TRM; CD8+CD103+) are recognized as a key player of anticancer immune response. To assess TRM cells in primary, metastatic, and recurrent head and neck squamous cell carcinoma (HNSCC), we developed a tissue microarray (TMA) and used multiplex IHC (MxIHC)., Experimental Design: Samples from primary tumors of 379 HNSCC cases treated at Southampton Hospitals between 2000 and 2016 were collected and analyzed. Of these, 105 cases had lymph node metastases and 82 recurrences. A TMA was generated with triplicate cores for each sample. MxIHC with a stain-and-strip approach was performed using CD8, CD103, and TIM3. Scanned slides were analyzed (digital image analysis) and quality checked (QC)., Results: After QC, 194 primary tumors, 76 lymph node metastases, and 65 recurrences were evaluable. Alcohol consumption was statistically significantly correlated with a reduction of TRM cells in primary tumors (nondrinker vs. heavy drinker: P = 0.0036). The known survival benefit of TRM cell infiltration in primary tumors was not found for lymph node metastasis. In recurrences, a high TRM cell number led to a favorable outcome after 12 months. The checkpoint molecule TIM3, was expressed significantly higher on TRM and non-TRM cells in the lymph node compared with primary tumors (P < 0.0001), which was also seen in recurrences (P = 0.0134 and P = 0.0007, respectively)., Conclusions: We confirm the prognostic impact of TIL in primary tumors and in recurrences. TRM cell density in lymph node metastases was not linked to outcome. The role of TIM3, as a therapeutic target remains to be defined., (©2023 American Association for Cancer Research.)

Fungicide resistance in foliar fungal pathogens is an increasing challenge to crop production. Yield impacts due to loss of fungicide efficacy may be reduced through effective surveillance and appropriate management intervention. For stubble-borne pathogens, off-season crop residues may be used to monitor fungicide resistance to inform pre-planting decisions; however, appropriate sampling strategies and support sizes for crop residues have not previously been considered. Here, we used Pyrenophora teres f. teres ( Ptt ) with resistance to demethylase inhibitor fungicides as a model system to assess spatial dependency and to compare the effects of different sampling strategies and support sizes on pathogen density ( Ptt DNA concentration) and the frequency of fungicide resistance mutation. The results showed that sampling strategies (hand-picked versus raked) did not affect estimates of pathogen density or fungicide resistance frequency; however, sample variances were lower from raked samples. The effects of differing sample support size, as the size of the collection area (1.2, 8.6, or 60 m 2 ), on fungicide resistance frequency were not evident ( P > 0.05). However, measures of pathogen density increased with area size ( P < 0.05); the 60 m 2 area yielded the highest Ptt DNA concentration and produced the lowest number of pathogen-absent samples. Sample variances for pathogen density and fungicide resistance frequency were generally homogeneous between area sizes. The pattern of pathogen density was spatially independent; however, spatial dependency was identified for fungicide resistance frequency, with a range of 110 m, in one of the two fields surveyed. Collectively, the results inform designs for monitoring of fungicide resistance in stubble-borne pathogens., Competing Interests: The author(s) declare no conflict of interest.

Background: The University of Southampton, in collaboration with the University Hospital Southampton (UHS) NHS Foundation Trust and industrial partners, has been at the forefront of developing three-dimensional (3D) imaging workflows using X-ray microfocus computed tomography (μCT) -based technology. This article presents the outcomes of these endeavours and highlights the distinctive characteristics of a μCT facility tailored explicitly for 3D X-ray Histology, with a primary focus on applications in biomedical research and preclinical and clinical studies., Methods: The UHS houses a unique 3D X-ray Histology (XRH) facility, offering a range of services to national and international clients. The facility employs specialised μCT equipment explicitly designed for histology applications, allowing whole-block XRH imaging of formalin-fixed and paraffin-embedded tissue specimens. It also enables correlative imaging by combining μCT imaging with other microscopy techniques, such as immunohistochemistry (IHC) and serial block-face scanning electron microscopy, as well as data visualisation, image quantification, and bespoke analysis., Results: Over the past seven years, the XRH facility has successfully completed over 120 projects in collaboration with researchers from 60 affiliations, resulting in numerous published manuscripts and conference proceedings. The facility has streamlined the μCT imaging process, improving productivity and enabling efficient acquisition of 3D datasets., Discussion & Conclusions: The 3D X-ray Histology (XRH) facility at UHS is a pioneering platform in the field of histology and biomedical imaging. To the best of our knowledge, it stands out as the world's first dedicated XRH facility, encompassing every aspect of the imaging process, from user support to data generation, analysis, training, archiving, and metadata generation. This article serves as a comprehensive guide for establishing similar XRH facilities, covering key aspects of facility setup and operation. Researchers and institutions interested in developing state-of-the-art histology and imaging facilities can utilise this resource to explore new frontiers in their research and discoveries., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Katsamenis OL et al.)

Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and unfolded protein response-dependent apoptosis of senescent cells, and knockdown of COPI subunits improves the outcomes of cancer and fibrosis in mouse models. Drugs targeting COPI have poor pharmacological properties, but we find that N-myristoyltransferase inhibitors (NMTi) phenocopy COPI inhibition and are potent senolytics. NMTi selectively eliminated senescent cells and improved outcomes in models of cancer and non-alcoholic steatohepatitis. Our results suggest that senescent cells rely on a hyperactive secretory apparatus and that inhibiting trafficking kills senescent cells with the potential to treat various senescence-associated diseases., (© 2023. The Author(s).)

Background: Enhanced Recovery After Surgery (ERAS) programs have become a mainstay of modern surgical care, and efforts to decrease postoperative opioid consumption have been increasingly employed. A previous study from our institution demonstrated that ERAS protocols decreased opioid use in the first 48 hours after surgery by 61%. In the present study, a lidocaine infusion was added for postoperative pain control. The aim was to analyze the differences in opioid requirements with and without this infusion in the first 48 hours after laparoscopic colectomy in ERAS patients., Methods: Retrospective review of patients was conducted at an academically affiliated tertiary care hospital. The population included patients undergoing elective laparoscopic colon surgery enrolled in the ERAS program with the implementation of a lidocaine drip from June 2019 to October 2019, and compared to a previous patient cohort of ERAS patients evaluated without the lidocaine drip from September 2015 to May 2018., Results: The primary endpoint was postoperative opioid use in the first 48 hours based on IV morphine milligram equivalents (MME). Secondary measures included type of surgery, age, BMI, prior abdominal surgery, and prior opioid use. Median MMEs were 6.0 in the lidocaine infusion group and 12.5 in the group without lidocaine, representing a 52% reduction (p < 0.001)., Discussion: This study demonstrates a significant reduction in post-op opioid use in ERAS patients who receive a lidocaine infusion after laparoscopic colectomy. Further studies should focus on measures to limit the treatment side effects in order to maximize the opioid-sparing benefits of this intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Oculocutaneous albinism (OCA) is a genetic disease caused by disorders in melanin synthesis or distribution. In this descriptive study conducted in a tertiary care pediatric hospital, patients with a clinical diagnosis of OCA and genetic study were retrospectively recruited and underwent dermatological and ophthalmological exam, including optical coherence tomography (OCT) and digital dermoscopy. Our findings revealed milder OCA phenotypic expression in individuals harboring single pathogenic mutations in conjunction with polymorphisms, as well as in those with mutations of uncertain significance. Regardless OCA subgroup, severe phenotypes of OCA were associated with a higher number of mutations/polymorphisms in melanin biosynthesis genes and paler dermoscopic patterns, such as vascular pattern, which was the most common pattern in our series., (© 2023 Wiley Periodicals LLC.)

An extensive literature review, combined with practical experience of forensic testing, has identified several concerns regarding existing studies into skin simulants. These can be summarised as arising due to human skin being a highly complex, multi-layered and anisotropic material whose mechanical properties depend on many factors such as age and gender of the host. In many studies (and papers) essential information is missing. Although there is some parallelism between the studies, the reported energy density at perforation is very inconsistent (a function of the natural variation of skin properties alluded to above) and differs from 0,113 J/mm 2 [1] to 0,239 J/mm 2 [2]. Which is, in fact, a more than 100 % variation. Such a variation is arguably insufficient to enable accurate replication with a single simulant material. Combined with the missing common agreement about the energy density threshold between countries, laboratories and researchers, this analysis clearly identifies the need for an adjustable and / or customizable skin simulant. To-date, the most often used simulation material for human skin in ballistic testing is 'Chrome crusted cow hide' [3]. However, this is a natural material and, consequently therefore, inevitably physically variable in nature - both inter and intra hide. Ballistic tests on 10 chrome crusted cow hides using 4,5 mm BB's gave v50% ranging from 113 m/s to 200 m/s, an uncontrolled variability for forensic experiments. Hence, the authors examined a skin analogue that could be produced in-house, enabling tailoring to match the desired properties, and with improved consistency. To this end, a thin, 4 mm thick, layer of gelatine (30 - 45 wt%, increasing per 1 wt%) was studied. The ballistic resistance of the gelatine skin analogue was compared to the v50%'s published values in literature, with good agreement found as the gelatine concentration was varied. In comparison to the chrome crusted cow hides this suggests that this relatively simple and accessible approach has potential to provide a more consistent standard., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest concerning this study., (Copyright © 2023. Published by Elsevier B.V.)

Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8 + T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1., Competing Interests: Declaration of interests The La Jolla Institute of Immunology has filed a patent “Methods for modulating an immune response to cancer or tumor cells” related to this work, and S.E., P.V., and C.H.O. are co-inventors on this patent., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Globally, yield losses associated with failed crop protection due to fungicide-resistant pathogens present an increasing problem. For stubble-borne pathogens, assessment of crop residues during the off-season could provide early fungicide resistance quantification for informed management decisions to mitigate yield losses. However, stubble assessment is hampered by assay inhibitors that are derived from decaying organic matter. To overcome assay inhibition from weathered stubble samples, we used a systems approach to quantify the frequency of resistance to demethylase inhibitor fungicides of the barley pathogen Pyrenophora teres f. teres . The system canvassed (i) 10 ball-milling conditions; (ii) four DNA extraction methodologies; and (iii) three column purification techniques for the provision of sufficient yield, quality, and purity of fungal DNA for a PCR-based fungicide resistance assay. Results show that DNA quantity and purity differed within each of the above three categories, with the optimized pipeline being (i) ball-milling samples in a 50-ml stainless steel canister for 5 min using a 20-mm ball at 30 revolutions s -1 ; (ii) a modified Brandfass method (extracted 64% more DNA than other methods assessed); and (iii) use of silica resin columns for the highest DNA concentration with optimal DNA purity. The chip-digital PCR assay, which quantified fungicide resistance from field samples, was unaffected by the DNA extraction method or purification technique, provided that thresholds of template quantity and purity were satisfied. In summary, this study has developed molecular pipeline options for pathogen fungicide resistance quantification from cereal stubbles, which can guide management for improved crop protection outcomes.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD). Trajectory inference identifies three phases of control tissue fibroblast activation, leading to myofibroblast enrichment in tumour samples: initial upregulation of inflammatory cytokines, followed by stress-response signalling and ultimately increased expression of fibrillar collagens. Myofibroblasts correlate with poor overall survival rates in LUAD, associated with loss of epithelial differentiation, TP53 mutations, proximal molecular subtypes and myeloid cell recruitment. In squamous carcinomas myofibroblasts were not prognostic despite being transcriptomically equivalent. These findings have important implications for developing fibroblast-targeting strategies for cancer therapy., (© 2023. The Author(s).)

The relatively recent developments in mass spectrometry (MS) have provided novel opportunities for this technology to impact modern medicine. One of those opportunities is in biomarker discovery and diagnostics. Key developments in sample preparation have enabled a greater range of clinical samples to be characterized at a deeper level using MS. While most of these developments have focused on blood, tissues have also been an important resource. Fresh tissues, however, are difficult to obtain for research purposes and require significant resources for long-term storage. There are millions of archived formalin-fixed paraffin-embedded (FFPE) tissues within pathology departments worldwide representing every possible tissue type including tumors that are rare or very small. Owing to the chemical technique used to preserve FFPE tissues, they were considered intractable to many newer proteomics techniques and primarily only useful for immunohistochemistry. In the past couple of decades, however, researchers have been able to develop methods to extract proteins from FFPE tissues in a form making them analyzable using state-of-the-art technologies such as MS and protein arrays. This review will discuss the history of these developments and provide examples of how they are currently being used to identify biomarkers and diagnose diseases such as cancer.

Myofibroblastic cancer-associated fibroblast (myoCAF)-rich tumors generally contain few T cells and respond poorly to immune-checkpoint blockade. Although myoCAFs are associated with poor outcome in most solid tumors, the molecular mechanisms regulating myoCAF accumulation remain unclear, limiting the potential for therapeutic intervention. Here, we identify ataxia-telangiectasia mutated (ATM) as a central regulator of the myoCAF phenotype. Differentiating myofibroblasts in vitro and myoCAFs cultured ex vivo display activated ATM signaling, and targeting ATM genetically or pharmacologically could suppress and reverse differentiation. ATM activation was regulated by the reactive oxygen species-producing enzyme NOX4, both through DNA damage and increased oxidative stress. Targeting fibroblast ATM in vivo suppressed myoCAF-rich tumor growth, promoted intratumoral CD8 T-cell infiltration, and potentiated the response to anti-PD-1 blockade and antitumor vaccination. This work identifies a novel pathway regulating myoCAF differentiation and provides a rationale for using ATM inhibitors to overcome CAF-mediated immunotherapy resistance., Significance: ATM signaling supports the differentiation of myoCAFs to suppress T-cell infiltration and antitumor immunity, supporting the potential clinical use of ATM inhibitors in combination with checkpoint inhibition in myoCAF-rich, immune-cold tumors., (©2022 The Authors; Published by the American Association for Cancer Research.)