Extricating human tumour immune alterations from tissue inflammation.

Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain1,2. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment3,4. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (Treg) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1+ Treg cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1- Treg cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns.

Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Where Are We Now and Where Are We Headed?

OPINION STATEMENT: Recently, the addition of PD-1 pathway targeting immune checkpoint inhibitors (ICI) to standard neoadjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) has been shown to improve rates of pathological complete response (pCR), as well as event-free survival regardless of attainment of pCR. Recurrent TNBC remains a devastating diagnosis and thus novel treatments that improve chance of cure in early-stage TNBC should be promptly integrated into standard of care paradigms. However, approximately 50% of patients with early TNBC will experience pCR with chemotherapy alone, and the addition of ICI carries the risk of sometimes permanent immune-related toxicities. This raises the critical question whether all early-stage TNBC patients should receive ICI in combination with neoadjuvant chemotherapy. As yet, there is no predictive biomarker to select patients most likely to benefit from ICI; however, it would seem that at least all node positive patients should receive an ICI with their neoadjuvant chemotherapy, on the basis of high clinical risk and potential to increase their pCR rate and ultimately the chance of cure. It is plausible that some lower-risk (stage I/II) TNBC demonstrating strong pre-existing immune activation (high tumor-infiltrating lymphocytes (TILs) and/or PD-L1 expression) may be successfully treated with ICI in combination with less cytotoxic chemotherapy, and this requires further evaluation in clinical trials. The contribution of the adjuvant phase of ICI on clinical benefit is unclear even in patients who do not achieve a pCR and long-term data from ongoing studies without adjuvant ICI component may help inform us on an appropriate strategy in the short term. Similarly, the potential benefit of other adjuvant therapies in patients with poor response to neoadjuvant ICI with chemotherapy, including capecitabine and olaparib with or without ICI, is also unknown, but is rational on the basis of administering a non-cross-resistant anti-tumour agent. In conclusion, the addition of neoadjuvant ICI to chemotherapy significantly improves both the quality and quantity of the anti-tumour T cell response, suggesting that improvements in recurrence-free survival occur through better immune protection from cancer. In the future, development of ICI agents that target tumour-specific T cells may favourably alter the toxicity profile, improving the risk-benefit ratio for survivors.

Triplet Therapy in Melanoma - Combined BRAF/MEK Inhibitors and Anti-PD-(L)1 Antibodies.

PURPOSE OF REVIEW: We provide an updated review of clinical trials evaluating the combination of BRAF/MEK inhibitors with anti-PD-(L)1 therapy (triplet therapy) for patients with advanced BRAF-mutant melanoma, accompanied by a summary of the biological evidence supporting this combination. RECENT FINDINGS: Resistance to BRAF/MEK inhibition and comparatively low response rates to immune checkpoint inhibitors remain clinical challenges in the treatment of melanoma. Preclinical data demonstrates that targeted therapy is immune-modulatory and synergises with immune checkpoint inhibition. Several randomised controlled trials have evaluated the combination of targeted therapy with immune checkpoint inhibition. Triplet therapy has shown improvements in progression-free survival and durability of response compared to BRAF/MEK inhibition alone; however, questions remain regarding the best clinical scenario for implementation of this regimen in the era of front-line immunotherapy.

Evaluation and management of rectal bleeding in pregnancy.

Rectal bleeding occurs in about 40% of pregnant women, and is predominantly attributed to benign perianal pathology (haemorrhoids or anal fissures). More sinister causes of rectal bleeding may be heralded by key red flag clinical and biochemical features. These features should be evaluated in all women with rectal bleeding. Imaging investigations or flexible sigmoidoscopy may be warranted. The latter can be performed safely by experienced operators in pregnant women. Women with evidence of haemodynamic compromise, elevated inflammatory markers, significant anaemia, signs of intestinal obstruction or compromise to the fetus should be evaluated urgently. Providers must be mindful of the changes in normal ranges for common haematological and biochemical parameters in pregnancy compared with the non-pregnant state. Faecal calprotectin is an established tool for identification of intestinal inflammation and is valid in pregnancy. An elevated faecal calprotectin level (≥ 50 µg/g) signifies a need for further diagnostic evaluation. Inflammatory bowel disease may present initially, or with worsening disease activity, in pregnancy. Expedient diagnosis with the use of faecal calprotectin, sigmoidoscopy with or without intestinal ultrasound, exclusion of alternative or compounding infective aetiologies, and institution of appropriate therapy are critical. Medical therapies for management of inflammatory bowel disease can be safely instituted in pregnancy. Colorectal cancer incidence is increasing in younger age groups, but fortunately remains rare. When diagnosed in pregnancy, colorectal cancer can be successfully and safely managed with a collaborative multidisciplinary team approach. Early diagnosis is key to optimising outcomes.

Brief Research Report: Prehospital Rapid Sequence Airway.

BACKGROUND: Rapid Sequence Airway (RSA) describes the administration of an induction agent and paralytic followed by the intended primary placement of an extraglottic airway device rather than an endotracheal tube. The purpose of this study was to determine the success rates for prehospital RSA. The secondary goal was to determine aspiration rates among patients managed with RSA. METHODS: Adult and pediatric prehospital RSA cases between 2005 and 2017 reported to an airway quality assurance registry from one ground and one air agency were reviewed. Success was defined as the ability to adequately ventilate patients after extraglottic device placement. Aspiration was defined as radiologic evidence (chest x-ray or CT scan) within 48 hours of hospital presentation. RESULTS: 68 patients underwent RSA with a King LTS-D (n = 24), LMA-Supreme (n = 28), Combitube (n = 2), LMA-Unique (n = 8) and iGel (n = 6). Age ranged from 1 year to 73 years with 10 patients less than 18. RSA was successful in 64 (94%) cases; 56 (88%) were successful on first pass and 63 (98%) within 2 attempts. The RSA procedure occurred in an aircraft in 14 (21%) of cases and 71% of patients were in cervical precautions. Duration of EGD insertion prior to hospital arrival ranged from 5 to 102 minutes with an average of 34.5 minutes. Aspiration data was available for 46 patients of whom 4 (8.7%) were found to have evidence of aspiration. CONCLUSION: Overall and first pass RSA success rates were high and aspiration rates were low in this quality assurance registry despite predictors of airway difficulty. RSA may be a reasonable alternative to RSI for prehospital airway management that merits further research.

Restorative design and associated risks for peri-implant diseases.

The prevalence of inflammatory conditions around dental implants is significant. Current analysis indicates that the rates for peri-mucositis and peri-implantitis may be as high as 40%-65% and 20%-47%, respectively. Over the last decade, many risk factors have been associated with peri-mucositis and peri-implantitis, creating a multifactorial disease etiology that complicates both diagnosis and treatment. Furthermore, additional considerations such as initial surgical implant placement position, disruption of the biologic interface associated with the implant-abutment interface manipulation, or prosthetic design may also influence the host response to commonly employed oral prostheses or the diagnosis of inflammatory states. Coupled with the temporal nature of disease progression around implants, understanding and accounting for these additional parameters may help reduce the number of variables that the surgeon/restorative team face when incorporating implant therapy into daily practice. Therefore, this review discusses the importance of surgical and restorative design by reviewing the concepts of natural and prosthetic emergence profile and implant design and position, as well as many other restorative concepts related to potential implant complications and disease. Understanding both the inflammatory nature of peri-implant disease and additional parameters related to both surgical and prosthetic procedures may provide the best possible approach to reducing the prevalence of both peri-mucositis and peri-implantitis within the realm of dental implant therapy.

Hypothalamic demyelination causing panhypopituitarism.

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic-pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic-pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab-related and primary pituitary pathology are discussed.

Evaluation of efficacy of prion reduction filters using blood from an endogenously infected 263K scrapie hamster model.

BACKGROUND: The P-Capt prion reduction filter (MacoPharma) removes prion infectivity in model systems. This independent evaluation assesses prion removal from endogenously infected animal blood, using CE-marked P-Capt filters, and replicates the proposed use of the filter within the UK Blood Services. STUDY DESIGN AND METHODS: Two units of blood, generated from 263K scrapie-infected hamsters, were processed using leukoreduction filters (LXT-quadruple, MacoPharma). Approximately 100 mL of the removed plasma was added back to the red blood cells (RBCs) and the blood was filtered through a P-Capt filter. Samples of unfiltered whole blood, the prion filter input (RBCs plus plasma and SAGM [RBCPS]), and prion-filtered leukoreduced blood (PFB) were injected intracranially into hamsters. Clinical symptoms were monitored for 500 ± 1 day, and brains were assessed for spongiosis and prion protein deposit. RESULTS: In Filtration Run 1, none of the 50 challenged animals were diagnosed with scrapie after inoculation with the RBCPS fraction, while two of 190 hamsters injected with PFB were infected. In Filtration Run 2, one of 49 animals injected with RBCPS and two of 193 hamsters injected with PFB were infected. Run 1 reduced the infectious dose (ID) by 1.467 log (>1.187 log and <0.280 log for leukoreduction and prion filtration, respectively). Run 2 reduced prion infectivity by 1.424 log (1.127 and 0.297 log, respectively). Residual infectivity was estimated at 0.212 ± 0.149 IDs/mL (Run 1) and 0.208 ± 0.147 IDs/mL (Run 2). CONCLUSION: Leukoreduction removed the majority of infectivity from 263K scrapie hamster blood. The P-Capt filter removed a proportion of the remaining infectivity, but residual infectivity was observed in two independent processes.

THE BARIATRIC AIRWAY. It's not all about the intubation.

In airway procedures, preparation is 90% of success. For obese patients, positioning is 90% of this preparation. Other considerations include utilizing NIPPV and nasal cannula apneic oxygenation, utilizing multiple providers and airway adjuncts for BVM ventilation, correctly dosing medications based upon ideal, lean or total body weight, and having backup airway devices ready.

Effect of rhBMP-2 dose on bone formation/maturation in a rat critical-size calvarial defect model.

BACKGROUND: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP-2 dose, frequency/severity of adverse events increasing with rising dose. OBJECTIVE: The objective of this study was to determine the most effective dose for rhBMP-2 soak-loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model. METHODS: One hundred sixty-eight outbred male Sprague-Dawley rats, age 11-13 weeks, weight 325-375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP-2/ACS into critical-size, ø8-mm, through-through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 µg rhBMP-2/defect, or serve as ACS or sham-surgery controls. RESULTS: rhBMP-2 dosages ≥ 2.5 µg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8-week healing interval. CONCLUSIONS: rhBMP-2/ACS accelerates local bone formation in the rat critical-size through-through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25-/2.5-µg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP-2 above the 2.5-µg dose. The 1.25-20.0 µg dose range did not invoke appreciable aberrant healing events.

Stem cells in regenerative dentistry: Current understanding and future directions.

BACKGROUND: Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications. HIGHLIGHTS: To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency. CONCLUSION: Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions.

Evaluation of a compression resistant matrix for recombinant human bone morphogenetic protein-2.

BACKGROUND: Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM). METHODS: Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/ß-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. RESULTS: Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm(2) , p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. CONCLUSIONS: rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s).

The value of long-term environmental monitoring programs: an Ohio River case study.

As a subset of environmental monitoring, fish sampling programs have been an important part of assessing the potential impacts of water withdrawals and effluent discharges on fish populations for many years. New environmental regulations often require that adverse environmental impacts to fish populations be minimized. Without long-term field data, population evaluations may incorrectly indicate adverse impacts where none exist or no impact where one is likely to occur. Several electric utility companies have funded the Ohio River Ecological Research Program, which has been in existence for over 40 years and consists of fish, habitat, and water quality studies at multiple power plant sites on the mainstem Ohio River. Sampling includes seasonal night-time electrofishing and daytime beach seining at three upstream and three downstream locations near each plant. The long-term nature of the program allows for the establishment of aquatic community indices to support evaluations of technology performance, the collaborative development of compliance metrics, and the assessment of fish population trends. Studies have concluded that the Ohio River fish community has improved in response to better water quality and that power plant fish entrainment and impingement and thermal discharges have had little or no measureable impact. Through collaboration and the use of long-term data, $6.3 million in monitoring costs have been saved during recent fish impingement studies. The ability to access a multiyear fish abundance database, with its associated data on age, growth, and fecundity, improves the quality of such evaluations and reduces the need for extensive field sampling at individual locations.

Integrating Immunotherapy Into the Treatment Landscape for Patients With Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive histologic subtype of breast cancer for which, until recently, treatment options have been limited to chemotherapy. In recent years, an improved understanding of the importance of tumor-infiltrating lymphocytes and the tumor microenvironment in TNBC has led to investigation of immune checkpoint inhibitors for treatment. There is now evidence from several randomized controlled trials that supports the addition of immune checkpoint inhibitors to first-line treatment of advanced TNBC and to neoadjuvant chemotherapy for stage II-III TNBC. In parallel, the PARP inhibitors have emerged as a targeted therapy option for patients with HER2-negative breast cancer harboring mutations in BRCA1, BRCA2, and PALB2. Here, we review the recent clinical trials that inform the integration of immune checkpoint inhibitors into treatments for TNBC and discuss ongoing challenges-including patient selection, management of resistance to post-checkpoint inhibitor therapy, and combining immunotherapy with targeted therapies, including PARP inhibitors.

American Academy of Periodontology best evidence consensus statement on the use of biologics in clinical practice.

A biologic is a therapeutic agent with biological activity that is administered to achieve an enhanced regenerative or reparative effect. The use of biologics has progressively become a core component of contemporary periodontal practice. However, some questions remain about their safety, indications, and effectiveness in specific clinical scenarios. Given their availability for routine clinical use and the existing amount of related evidence, the goal of this American Academy of Periodontology (AAP) best evidence consensus (BEC) was to provide a state-of-the-art, evidence-based perspective on the therapeutic application of autologous blood-derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet-derived growth factor BB (rhPDGF-BB), and recombinant human bone morphogenetic protein 2 (rhBMP-2). A panel of experts with extensive knowledge on the science and clinical application of biologics was convened. Three systematic reviews covering the areas of periodontal plastic surgery, treatment of infrabony defects, and alveolar ridge preservation/reconstruction and implant site development were conducted a priori and provided the foundation for the deliberations. The expert panel debated the merits of published data and exchanged experiential information to formulate evidence-based consensus statements and recommendations for clinical practice and future research. Based on an analysis of the current evidence and expert opinion, the panel concluded that the appropriate use of biologics in periodontal practice is generally safe and provides added benefits to conventional treatment approaches. However, therapeutic benefits and risks range based on the specific biologics used as well as patient-related local and systemic factors. Given the limited evidence available for some indications (e.g., gingival augmentation therapy, alveolar ridge preservation/reconstruction, and implant site development), future clinical studies that can expand the knowledge base on the clinical use of biologics in periodontal practice are warranted.

Safety of air medical transport of patients with COVID-19 by personnel using routine personal protective equipment.

OBJECTIVE: Air medical transport of patients with known or suspected coronavirus disease 2019 (COVID-19) likely represents a high-risk exposure to crew members as aircraft cabins are quite small resulting in close personal contact. The actual risk to medical crew members is not known. METHODS: We conducted an institutional review board-exempt, retrospective study of air medical transport of patients with known or suspected COVID-19 by 8 programs in the Four Corners Region to determine the number of symptomatic COVID-19 among air medical crew members compared to total exposure time. All programs used similar routine personal protective equipment (PPE), including N-95 masks and eye protection. Total exposure time was considered from time of first patient contact until handoff at a receiving hospital. RESULTS: There were 616 air transports: 62% by fixed-wing and 38% by rotor-wing aircraft between March 15 and September 6, 2020. Among transported patients, 407 (66%) were confirmed COVID+ and 209 (34%) were under investigation. Patient contact time ranged from 38 to 432 minutes with an average of 140 minutes. The total exposure time for medical crew was 2924 hours; exposure time to confirmed COVID+ patients was 2008 hours. Only 30% of patients were intubated, and the remainder had no oxygen (8%), low-flow nasal cannula (42%), mask (11%), high-flow nasal cannula (4.5%), and continuous positive airway pressure or bilevel positive airway pressure (3.5%). Two flight crew members out of 108 developed COVID that was presumed related to work. CONCLUSIONS: Air medical transport of patients with known or suspected COVID-19 using routine PPE is considered effective for protecting medical crew members, even when patients are not intubated. This has implications for health care personnel in any setting that involves care of patients with COVID-19 in similarly confined spaces.

A modified tensionless gingival grafting technique using acellular dermal matrix.

Conventional surgical procedures designed for autogenous tissue material may not be appropriate when using acellular dermal matrix (ADM) for the treatment of gingival recessions. This article describes a new surgical technique that addresses the unique and sensitive aspects of ADM specifically to improve esthetic outcomes and gain increased clinical predictability when treating Miller Class I and II gingival recession defects. In this paper, a root coverage case is described and the specific steps and rationale for this new technique are explained. This technique has been predictable clinically, with results comparable to those achieved using autogenous tissue.

Sectional Connective Tissue Technique Combined With an Emergence Profile Provisional for Gingival Margin Stabilization During Immediate Implant Placement: A Case Report With a 2-Year Follow-Up.

INTRODUCTION: Little is known regarding maintaining free gingival margin stability after immediate implant placement. Therefore, we present a sequential technique incorporating a sectional connective tissue graft with an emergence tissue provisional to stabilize the free gingival margin position during immediate implant placement in the esthetic zone. CASE PRESENTATION: A 57-year-old male was referred for assessment and treatment of a failing maxillary right central incisor. Clinical examination revealed poor retentive features, recurrent caries, and exposed endodontic material rendering a poor prognosis for the remaining tooth root system. After comprehensive evaluation, as well as understanding important patient case expectations, a decision was made to remove the existing tooth and place an immediate implant with a staged-provisional approach. To maintain the free gingival mid-facial height, a sectional-connective tissue graft technique was used concurrently with a custom emergence profile provisional to stabilize the gingiva immediately post-implant placement. CONCLUSION: Patients undergoing implant replacement of failing anterior maxillary teeth are at risk of esthetic complications. Marginal stability of the facial gingival is an important component of establishing and maintaining the final esthetic outcome. In cases where the initial hard or soft tissue thickness may put the patient at risk, combining soft and hard tissue augmentation with attention to emergence profile provisionalization appears to aid in the initial stability of the buccal free gingival margin. This report details the steps associated with a sectional connective tissue technique combined with emergence profile provisonalization and characterizes the gingival stability up to 2.5 years obtained with this approach.

Inflammatory Cytokines Induce Sustained CTLA-4 Cell Surface Expression on Human MAIT Cells.

Mucosal-associated invariant T (MAIT) cells acquire effector function in response to proinflammatory signals, which synergize with TCR-mediated signals. We asked if cell-intrinsic regulatory mechanisms exist to curtail MAIT cell effector function akin to the activation-induced expression of inhibitory receptors by conventional T cells. We examined human MAIT cells from blood and oral mucosal tissues by RNA sequencing and found differential expression of immunoregulatory genes, including CTLA-4, by MAIT cells isolated from tissue. Using an ex vivo experimental setup, we demonstrate that inflammatory cytokines were sufficient to induce CTLA-4 expression on the MAIT cell surface in the absence of TCR signals. Even brief exposure to the cytokines IL-12, IL-15, and IL-18 was sufficient for sustained CTLA-4 expression by MAIT cells. These data suggest that control of CTLA-4 expression is fundamentally different between MAIT cells and conventional T cells. We propose that this mechanism serves to limit MAIT cell-mediated tissue damage.