Morphology and volume of Meibomian glands ex vivo pre and post partial tarsal plate excision, cryotherapy and laser therapy in the dog using microCT.

OBJECTIVE: To determine the morphology and volume of Meibomian glands (MG) of dogs with microCT before and after partial tarsal plate excision (PTPE), cryotherapy, and laser therapy. PROCEDURE: MicroCT scans were made of 12 upper lids (ULs) and lower lids (LLs) of 12 dogs. After undergoing PTPE, 10 ULs and LLs were scanned again, and one UL and one LL was scanned after laser therapy and one UL and one LL after cryotherapy. RESULTS: The length of the area containing MGs did not change pre- and post-PTPE, and cryo- or laser therapy. The mean number of MGs in the ULs and LLs was 30.50 and 29.42, respectively, and did not change during the procedures. The average length of one individual MG was 2.60 mm. The mean volume of MGs in the 10 ULs and LLs pre-PTPE was 21.45 and 17.2 mm3 , respectively, and 12.84 and 11.25 mm3 in the UL and LL after PTPE, respectively. The mean volume of MGs decreased from 29.78 mm3 precryotherapy to 28.91 mm3 post-treatment and in the lower eyelid from 22.87 to 22.4 mm3 after cryotherapy. The mean volume of MGs in the UL and LL before laser therapy was 8.95 and 6.78 mm3 , respectively, and after 9.25 and 6.38 mm3 , respectively. CONCLUSION: MicroCT is a valuable tool to determine the morphology and the volume of MGs and to demonstrate changes that occur after PTPE, laser-, and cryotherapy. There is no need for additional preparation, such as staining, of the specimen prior to scanning.

Novel 3D in situ visualization of seal heartworm (Acanthocheilonema spirocauda) larvae in the seal louse (Echinophthirius horridus) by X-ray microCT.

The seal heartworm Acanthocheilonema spirocauda (Nematoda: Onchocercidae) parasitizes the heart and pulmonary arteries of various phocid seals of the Northern Hemisphere. Over many decades, potential vectors of this parasite have been discussed, and to this date, the life cycle is not fully known. The seal louse Echinophthirius horridus (Anoplura: Echinophthiriidae) is an obligatory, permanent and haematophagous ectoparasite of phocids that has been hypothesized to function as obligate intermediate host for A. spirocauda. We examined 11 adult E. horridus specimens collected from stranded harbour seals (Phoca vitulina) in rehabilitation at the Sealcentre Pieterburen by X-ray microCT imaging, aiming to illustrate larval A. spirocauda infection sites in situ. In three of these specimens, thread-like larvae were detected in insect organs. Detailed imaging of the most infected louse revealed a total of 54 A. spirocauda larvae located either in fat bodies or the haemocoel. Histological analysis of the same specimen illustrated nematode cross-sections, confirming X-ray microCT data. The current data strongly suggest that E. horridus is a natural intermediate host for A. spirocauda. Moreover, we demonstrate the potential of X-ray microCT-based imaging as a non-destructive method to analyze host-parasite interactions, especially in the neglected field of marine mammal parasitology.

Endodontic Treatment of a Traumatic Tusk Fracture With Exposed Pulp in an Asian Elephant (Elephas maximus).

Tusk fracture in elephants is a common incident often resulting in pulp exposure and pulpitis. Extensive lavage, endodontic therapy, direct pulp capping, or extraction are treatment options. In this report, the successful management of a broken tusk of a juvenile male Asian elephant (Elephas maximus) including morphological analysis of the tusk tip 2 years after surgery are presented. Treatment was carried out under barn conditions and included antimicrobial photodynamic therapy and partial pulpotomy with direct pulp capping. Immediate pain relief was reached. The fractured tusk was preserved and continued to grow. The therapeutic filling material remained intact for over 1 year but was absent 2 years after treatment. The former pulp cavity of the tusk tip was filled with reparative dentin, osteodentin, and bone, but the seal between these hard tissues and pulp chamber dentin was incomplete. Radiographs obtained 3 years after treatment showed no differences in pulp shape, pulp width, and secondary dentin formation between the treated right and the healthy left tusk. It can be concluded that in case of an emergency, the endodontic therapy of a broken elephant tusk can be attempted under improvised conditions with adequate success. Photodynamic therapy might contribute to prevent infection and inflammation of the pulp. The decision tree published by Steenkamp (2019) provides a valuable tool to make quick decisions regarding a suitable therapy of broken tusks.

Comparison of a novel extracapsular suture technique with a standard fabellotibial suture technique for cranial cruciate ligament repair using a custom-made limb-press model in cats.

OBJECTIVES: The aim of our study was to compare the standard fabellotibial suture with Mini TightRope fixation for the treatment of a cranial cruciate ligament (CCL) rupture using a feline custom-made limb press. METHODS: Cadaveric hindlimbs of 10 cats were inserted in the limb press at predefined joint angles and loads of 10% and 30% body weight (BW) were applied. Mediolateral radiographs were taken and three-dimensional coordinates were recorded using a microscribe digitiser, with intact and transected CCLs and after either fabellotibial suture or Mini TightRope fixation were performed. Different distances and angles from radiographs or microscribe coordinates were analysed. RESULTS: Radiographic distances from the femoral condyle to the cranial edge of the tibia (X1-X2) were higher in CCL-deficient stifles than in intact stifles at 10% and 30% BW loads. All fabellotibial sutures and Mini TightRope fixations neutralised excessive cranial tibial thrust. A significant difference in the distance between the patella and tibial tuberosity (D2) was observed between CCL-deficient limbs and Mini TightRope-fixed limbs at 10% BW load (P <0.04). A significant difference in the distance between the tibial tuberosity and lateral collateral ligament of the femur (D3) was observed between the intact and transected CCLs on the left legs at 10% BW load (P <0.003) and on both legs at 30% BW load (P <0.002). Furthermore, we observed significant differences between CCL-deficient left legs and Mini TightRope-treated legs at 10% BW load (P <0.003). With regard to fabellotibial suture-treated legs, we observed significant differences between transected limbs and fixed limbs at 30% BW load (P <0.004). W1 (craniocaudal angle) and W2 (mediolateral angle) showed significant differences between intact and transected CCLs and between transected and fixed limbs at 30% BW load (P <0.004). CONCLUSIONS AND RELEVANCE: Fixation of CCL-deficient stifles with lateral fabellotibial suture, as well as Mini TightRope tightened with a 20 N load, produces good biomechanical stability, as detected via radiographic assessment.

Diagnostic Yield of Micro-Computed Tomography (micro-CT) Versus Histopathology of a Canine Oral Fibrosarcoma.

Micro-computed tomography (micro-CT) imaging currently gains increased interest in human as well as veterinary medicine. The ability to image 3-dimensional (3D) biopsy specimens nondestructively down to 1 µm spatial resolution makes it a promising tool for microscopic tissue evaluation in addition to histopathology. Visualizing tumor margins and calculating tumor load on 3D reconstructions may also enhance oncological therapies. The objective of this study was to describe the workflow from tumor resection to histopathological diagnosis, using both routine hematoxylin-eosin (HE)-stained sections and micro-CT tomograms on a stage II oral fibrosarcoma in a 7-year-old Hovawart dog. The maxillectomy specimen was fixed with formalin and stained with an X-ray dense soft tissue contrast agent. Micro-CT imaging was done using an ex vivo specimen micro-CT device. Tumor margins could not be exactly determined on micro-CT tomograms due to limited image resolution and contrast. Histopathology was performed after washing out the contrast agent. It showed neoplastic cells infiltrating the surrounding tissue further than assumed from micro-CT images. A total tumor volume of 10.3 cm3 could be calculated based on correlating micro-CT tomograms with HE-stained sections. This correlative approach may be of particular interest for oncological therapy. More than that, micro-CT imaging technology supported histopathology by means of 3D orientation and selection of slices to be cut on determining tumor margins. In this clinical case report, micro-CT imaging did not provide unambiguous clinical evidence for oncological decision-making, but it showed potential to support histopathology and calculate tumor volume for further clinical use.

Finite Element Modelling Simulated Meniscus Translocation and Deformation during Locomotion of the Equine Stifle.

We developed a finite element model (FEM) of the equine stifle joint to identify pressure peaks and simulate translocation and deformation of the menisci. A series of sectional magnetic resonance images (1.5 T) of the stifle joint of a 23 year old Shetland pony gelding served as basis for image segmentation. Based on the 3D polygon models of femur, tibia, articular cartilages, menisci, collateral ligaments and the meniscotibial ligaments, an FEM model was generated. Tissue material properties were assigned based on data from human (Open knee(s) project) and bovine femoro-tibial joint available in the literature. The FEM model was tested across a range of motion of approximately 30°. Pressure load was overall higher in the lateral meniscus than in the medial. Accordingly, the simulation showed higher translocation and deformation in the lateral compared to the medial meniscus. The results encourage further refinement of this model for studying loading patterns on menisci and articular cartilages as well as the resulting mechanical stress in the subchondral bone (femur and tibia). A functional FEM model can not only help identify segments in the stifle which are predisposed to injury, but also to better understand the progression of certain stifle disorders, simulate treatment/surgery effects and to optimize implant/transplant properties.

Drafting a Surgical Procedure Using a Computational Anatomy Driven Approach for Precise, Robust, and Safe Vestibular Neuroprosthesis Placement-When One Size Does Not Fit All.

OBJECTIVE: To design and evaluate a new vestibular implant and surgical procedure that should reach correct electrode placement in 95% of patients in silico. DESIGN: Computational anatomy driven implant and surgery design study. SETTING: Tertiary referral center. PARTICIPANTS: The population comprised 81 patients that had undergone a CT scan of the Mastoid region in the Maastricht University Medical Center. The population was subdivided in a vestibular implant eligible group (28) and a control group (53) without known vestibular loss. INTERVENTIONS: Canal lengths and relationships between landmarks were calculated for every patient. The relationships in group-anatomy were used to model a fenestration site on all three semicircular canals. Each patient's simulated individual distance from the fenestration site to the ampulla was calculated and compared with the populations average to determine if placement would be successful. MAIN OUTCOME MEASURES: Lengths of the semicircular canals, distances from fenestration site to ampulla (intralabyrinthine electrode length), and rate of successful electrode placement (robustness). RESULTS: The canal lengths for the lateral, posterior, and superior canal were respectively 12.1 mm ±â€Š1.07, 18.8 mm ±â€Š1.62, and 17.5 mm ±â€Š1.23, the distances from electrode fenestration site to the ampulla were respectively 3.73 mm ±â€Š0.53, 9.02 mm ±â€Š0.90, and 5.31 mm ±â€Š0.73 and electrode insertions were successful for each respective semicircular canal in 92.6%, 66.7%, and 86.4% of insertions in silico. The implant electrode was subsequently revised to include two more electrodes per lead, resulting in a robustness of 100%. CONCLUSIONS: The computational anatomy approach can be used to design and test surgical procedures. With small changes in electrode design, the proposed surgical procedure's target robustness was reached.

Surgical enlargement of the nasomaxillary aperture and transnasal conchotomy of the ventral conchal sinus: Two surgical techniques to improve sinus drainage in horses.

OBJECTIVE: To evaluate 2 surgical techniques for establishing and/or improving paranasal sinus drainage in cadaver heads and horses with sinusitis and evaluate the feasibility of postoperative transnasal sinus endoscopy. STUDY DESIGN: Ex vivo study (equine cadaver heads) and case series. SAMPLE POPULATION: Nine adult equine cadaver heads and 8 horses with recurrent sinusitis. METHODS: For the ex vivo study, the following procedures were performed on 9 cadaver heads: preoperative and postoperative computed tomography (heads 1-6), endoscopy-guided transnasal conchotomy of the ventral conchal sinus (TCVCS) and surgical enlargement of the nasomaxillary aperture (SENMAP) on opposite sides (heads 1-3), combined TCVCS and SENMAP on both sides (heads 4-9), evaluation of sinus drainage before and after surgery (heads 7-9), and postoperative transnasal endoscopy (heads 4-9). For the case series, 8 horses with secondary sinusitis were treated in standing position with SENMAP and/or TCVCS and postoperative transnasal endoscopy. RESULTS: Sinonasal communications were successfully created in all cadavers and affected live horses. Transnasal endoscopy of all sinuses except the middle conchal sinus was possible in heads 4-9 and in all clinical cases. Sinus drainage was improved (P = .028) by combining techniques. Blood loss in live horses ranged from 0.5-5.5 L (1.95 ± 1.5) per horse. Sinusitis resolved in all affected horses during follow-up of 3.2-25.5 months (13.5 ± 8.5). CONCLUSION: Transnasal conchotomy of the ventral conchal sinus and SENMAP consistently created large sinonasal communications, facilitating sinus endoscopy and improving sinus drainage. CLINICAL SIGNIFICANCE: Transnasal conchotomy of the ventral conchal sinus and SENMAP are viable options to treat horses with sinusitis and anatomical obstructions of the sinonasal communications.

Loss of Ing3 Expression Results in Growth Retardation and Embryonic Death.

The ING3 candidate tumour suppressor belongs to a family of histone modifying proteins involved in regulating cell proliferation, senescence, apoptosis, chromatin remodeling, and DNA repair. It is a stoichiometric member of the minimal NuA4 histone acetyl transferase (HAT) complex consisting of EAF6, EPC1, ING3, and TIP60. This complex is responsible for the transcription of an essential cascade of genes involved in embryonic development and in tumour suppression. ING3 has been linked to head and neck and hepatocellular cancers, although its status as a tumour suppressor has not been well established. Recent studies suggest a pro-metastasis role in prostate cancer progression. Here, we describe a transgenic mouse strain with insertional mutation of an UbC-mCherry expression cassette into the endogenous Ing3 locus, resulting in the disruption of ING3 protein expression. Homozygous mutants are embryonically lethal, display growth retardation, and severe developmental disorders. At embryonic day (E) 10.5, the last time point viable homozygous embryos were found, they were approximately half the size of heterozygous mice that develop normally. µCT analysis revealed a developmental defect in neural tube closure, resulting in the failure of formation of closed primary brain vesicles in homozygous mid-gestation embryos. This is consistent with high ING3 expression levels in the embryonic brains of heterozygous and wild type mice and its lack in homozygous mutant embryos that show a lack of ectodermal differentiation. Our data provide direct evidence that ING3 is an essential factor for normal embryonic development and that it plays a fundamental role in prenatal brain formation.

Morphology of the bryozoan Cinctipora elegans (Cyclostomata, Cinctiporidae) with first data on its sexual reproduction and the cyclostome neuro-muscular system.

BACKGROUND: Cyclostome bryozoans are an ancient group of marine colonial suspension-feeders comprising approximately 700 extant species. Previous morphological studies are mainly restricted to skeletal characters whereas data on soft tissues obtained by state-of-the-art methods are still lacking. In order to contribute to issues related to cyclostome ground pattern reconstruction, we analyzed the morphology of the neuromuscular system Cinctipora elegans by means of immunocytochemical staining, confocal laser scanning microscopy, histological sections and microCT imaging. RESULTS: Polypides of C. elegans are located in elongated tubular skeletal cystids. Distally, the orifice leads into a prominent vestibulum which is lined by an epithelium that joins an almost complete perimetrical attachment organ, both containing radially arranged neurite bundles and muscles. Centrally, the prominent atrial sphincter separates the vestibulum from the atrium. The latter is enclosed by the tentacle sheath which contains few longitudinal muscle fibers and two principal neurite bundles. These emerge from the cerebral ganglion, which is located at the lophophoral base. Lateral ganglia are located next to the cerebral ganglion from which the visceral neurite bundles emerge that extend proximally towards the foregut. There are four tentacle neurite bundles that emerge from the ganglia and the circum-oral nerve ring, which encompasses the pharynx. The tentacles possess two striated longitudinal muscles. Short buccal dilatators are situated at the lophophoral base and short muscular sets are present at the abfrontal and frontal side of the tentacle base. The pharynx is myoepithelial and triradiate in cross-section. Oocytes are found inside the pharyngeal myoepithelium. The digestive tract contains dense circular musculature and few longitudinal muscles. The membranous sac contains regular, thin, circular and diagonal muscles and neurites in its epithelial lining. CONCLUSIONS: The general structure of the neuro-muscular system is more reminiscent of the condition found in Gymnolaemata rather than Phylactolaemata, which supports a close relationship between Cyclostomata and Gymnolaemata. Several characters of C. elegans such as the lateral ganglia or loss of the cardia are probably apomorphic for this species. For the first time, oocytes that surprisingly develop in the pharyngeal wall are reported for this species.

Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction.

The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized. AMG161 inhibits human and chimeric but not murine RANKL. To dissect the pathophysiological role of RANKL derived from hematopoietic and mesenchymal cells, we selectively exchanged the hematopoietic cell compartment by lethal irradiation and across-genotype bone marrow transplantation between wild-type and huRANKL-KI mice, exploiting the specificity of AMG161. After permanent coronary artery ligation, mice were injected with AMG161 or an isotype control antibody over 4 weeks post-MI. MI increased RANKL expression mainly in cardiomyocytes and scar-infiltrating cells 4 weeks after MI. Only inhibition of RANKL derived from hematopoietic cellular sources, but not global or mesenchymal RANKL inhibition, improved post-infarct survival and cardiac function. Mechanistically, hematopoietic RANKL inhibition reduced expression of the pro-inflammatory cytokine IL-1ß in the cardiac cellular infiltrate. In conclusion, inhibition of RANKL derived from hematopoietic cellular sources is beneficial to maintain post-ischemic cardiac function by reduction of pro-inflammatory cytokine production. KEY MESSAGES: Experimental myocardial infarction (MI) augments cardiac RANKL expression in mice. RANKL expression is increased in cardiomyocytes and scar-infiltrating cells after MI. Global or mesenchymal cell RANKL inhibition has no influence on cardiac function after MI. Inhibition of RANKL derived from hematopoietic cells improves heart function post-MI. Hematopoietic RANKL inhibition reduces pro-inflammatory cytokines in scar-infiltrating cells.

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRasG12D in mouse lung epithelial cells markedly impairs the progression of KRasG12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRasG12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer.

Application of a Parallelizable Perfusion Bioreactor for Physiologic 3D Cell Culture.

It is crucial but challenging to keep physiologic conditions during the cultivation of 3D cell scaffold constructs for the optimization of 3D cell culture processes. Therefore, we demonstrate the benefits of a recently developed miniaturized perfusion bioreactor together with a specialized incubator system that allows for the cultivation of multiple samples while screening different conditions. Hence, a decellularized bone matrix was tested towards its suitability for 3D osteogenic differentiation under flow perfusion conditions. Subsequently, physiologic shear stress and hydrostatic pressure (HP) conditions were optimized for osteogenic differentiation of human mesenchymal stem cells (MSCs). X-ray computed microtomography and scanning electron microscopy (SEM) revealed a closed cell layer covering the entire matrix. Osteogenic differentiation assessed by alkaline phosphatase activity and SEM was found to be increased in all dynamic conditions. Furthermore, screening of different fluid shear stress (FSS) conditions revealed 1.5 mL/min (equivalent to ∼10 mPa shear stress) to be optimal. However, no distinct effect of HP compared to flow perfusion without HP on osteogenic differentiation was observed. Notably, throughout all experiments, cells cultivated under FSS or HP conditions displayed increased osteogenic differentiation, which underlines the importance of physiologic conditions. In conclusion, the bioreactor system was used for biomaterial testing and to develop and optimize a 3D cell culture process for the osteogenic differentiation of MSCs. Due to its versatility and higher throughput efficiency, we hypothesize that this bioreactor/incubator system will advance the development and optimization of a variety of 3D cell culture processes.

Osteoblast-specific overexpression of amphiregulin leads to transient increase in femoral cancellous bone mass in mice.

The epidermal growth factor receptor ligand amphiregulin (AREG) has been implicated in bone physiology and in bone anabolism mediated by intermittent parathyroid hormone treatment. However, the functions of AREG in bone have been only incipiently evaluated in vivo. Here, we generated transgenic mice overexpressing AREG specifically in osteoblasts (Col1-Areg). pQCT analysis of the femoral metaphysis revealed increased trabecular bone mass at 4, 8, and 10weeks of age in Col1-Areg mice compared to control littermates. However, the high bone mass phenotype was transient and disappeared in older animals. Micro-CT analysis of the secondary spongiosa confirmed increased trabecular bone volume and trabecular number in the distal femur of 4-week-old AREG-tg mice compared to control littermates. Furthermore, µ-CT analysis of the primary spongiosa revealed unaltered production of new bone trabeculae in distal femora of Col1-Areg mice. Histomorphometric analysis revealed a reduced number of osteoclasts in 4-week-old Col1-Areg mice, but not at later time points. Cancellous bone formation rate remained unchanged in Col1-Areg mice at all time points. In addition, bone mass and bone turnover in lumbar vertebral bodies were similar in Col1-Areg and control mice at all ages examined. Proliferation and differentiation of osteoblasts isolated from neonatal calvariae did not differ between Col1-Areg and control mice. Taken together, these data suggest that AREG overexpression in osteoblasts induces a transient high bone mass phenotype in the trabecular compartment of the appendicular skeleton by a growth-related, non-cell autonomous mechanism, leading to a positive bone balance with unchanged bone formation and lowered bone resorption.

Insights into the organization of plumatellid larvae (lophotrochozoa, Bryozoa) by means of 3D-imaging and confocal microscopy.

Within the Lophotrochozoa, the Bryozoa or Ectoprocta remain one of the phyla whose phylogenetic relation to other lophotrochozoans is still controversely discussed. To complement existing data and to gain more insight into bryozoan character evolution, we analyzed the morphology of the larva of the phylactolaemate Plumatella sp. The larva of Plumatella spp. consists of an outer ciliated mantle that covers two differentiated polypides. The muscular and serotonergic nervous system of the polypides correspond to previous studies. The two polypides and their corresponding buds differ in size, which, together with a comparison among bryozoans, indicates that a single polypide is the basal condition. The whole larval mantle and mantle fold are supplied with circular and longitudinal muscles, the former being more pronounced in the mantle fold. The apical plate on the anterior side contains a diffuse mesh of crossing fibers and thus differs from previous descriptions, which recognized a regular muscular grid. The serotonergic nervous system in the mantle and mantle fold consists of a diffuse basiepidermal nerve net with its highest concentration at the apical plate. Serotonin immunoreactivity so far has not been detected in the mantle fold. However, the presence of other neurotransmitters in the mantle fold shown by previous studies indicates that this nerve net is a common feature of phylactolaemate larvae. The main difference between currently analyzed phylactolaemate larvae seems to be the complexity of the larval mantle musculature, which most likely plays an important role during metamorphosis. This study confirms previous interpretations that the apical plate pole does not correspond to the apical pole of gymnolaemate larvae but to their oral side. Accelerated asexual development on the aboral pole leads to the suggestion that an apical organ is never formed and the apical plate compensates for its absence in the free-swimming period.

A dual role for autophagy in a murine model of lung cancer.

Autophagy is a mechanism by which starving cells can control their energy requirements and metabolic states, thus facilitating the survival of cells in stressful environments, in particular in the pathogenesis of cancer. Here we report that tissue-specific inactivation of Atg5, essential for the formation of autophagosomes, markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage of tumour-bearing mice. Autophagy-defective lung cancers exhibit impaired mitochondrial energy homoeostasis, oxidative stress and a constitutively active DNA damage response. Genetic deletion of the tumour suppressor p53 reinstates cancer progression of autophagy-deficient tumours. Although there is improved survival, the onset of Atg5-mutant KRas(G12D)-driven lung tumours is markedly accelerated. Mechanistically, increased oncogenesis maps to regulatory T cells. These results demonstrate that, in KRas(G12D)-driven lung cancer, Atg5-regulated autophagy accelerates tumour progression; however, autophagy also represses early oncogenesis, suggesting a link between deregulated autophagy and regulatory T cell controlled anticancer immunity.