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e16167 Background: Guidelines recommend systemic therapy for uHCC ineligible for locoregional therapy. Until the approval of tremelimumab + durvalumab for uHCC, in Oct 2022, 1L systemic therapies in the US included multikinase inhibitors and atezolizumab (A) + bevacizumab (B). It is crucial to understand factors driving real-world treatment decisions and outcomes in uHCC. Methods: Data were collected from electronic medical records from US Mayo Clinic sites. Pts with uHCC who initiated a 1L systemic therapy between Jun 2020–Oct 2022 (A + B was the only approved 1L immunotherapy (IO)-based regimen) with ≥2 follow-up visits, were included. Index was the date of first 1L systemic therapy. Pts were assessed by risk of post-index gastrointestinal (GI) bleeding (Child-Pugh class B or C, pre-index GI bleeding, uncontrolled hypertension [HTN] [≥2 anti-HTN drugs or ≥2 vital entries of SBP > 140 mmHg or DBP > 90 mmHg]), or significant varices and band ligation). Treatment patterns, overall survival (OS), and post-index GI bleeding were assessed. Results: A total of 186 pts met the inclusion criteria. Most common etiologies of liver disease were MASH (42.7%) and hepatitis C virus (40.2%). Pre-index GI bleeding was reported in 29.0% of pts, of which 46.3% occurred within 6 months (mo) pre-index; 62.4% of pts had EGD, of which 72.4% had varices. There were 128 (68.8%) pts with GI bleeding risk and 58 (31.2%) pts without GI bleeding risk. The most common 1L systemic therapies for pts with GI bleeding risk were A + B (72.7%) and A only (9.4%), while for pts without GI bleeding risk, A + B (29.3%), nivolumab + ipilimumab (13.8%), and B + chemotherapy (12.1%) were the most common. Median OS and OS rates at 12, 18, and 24 mo were lower, and post-index GI bleeding rate was higher in pts with vs without GI bleeding risk (Table). For pts treated with A + B, median OS and OS rates at 12, 18, and 24 mo were lower in pts with vs without GI bleeding risk (Table). Conclusions: In this network, prior to the approval of other 1L IO-based regimens for uHCC, many pts received A + B, despite risk of post-index GI bleeding. Median OS with A + B was shorter in pts with vs without GI bleeding risk. Data highlight the complexity of uHCC and the unmet need for guidance on characteristics-driven treatment decisions. © 2025 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Gastrointestinal Cancers Symposium. All rights reserved. Table. Full cohort A + B cohort All ptsN=186 GI bleeding risk N=128 No GI bleeding risk N=58 All pts N=110 GI bleeding risk N=93 No GI bleeding risk N=17 Median follow-up, mo 20.6 20.9 20.4 21.3 21.6 20.3 Median OS, mo 14.4 11.4 40.3 13.9 12.8 Not reached OS rates, % 12 mo 55.2 48.9 68.9 55.2 52.3 70.6 18 mo 45.3 38.1 61.1 44.1 41.6 57.8 24 mo 39.4 31.8 56.8 37.1 34.6 51.3 Post-index GI bleed, % 17.2 23.4 3.4 17.3 19.4 5.9

4020 Background: In previously treated patients (pts) with advanced extra-pancreatic NET (epNET) or pancreatic NET (pNET), cabozantinib (cabo) demonstrated improved progression-free survival compared to placebo (pbo) in the CABINET trial (NCT03375320). Here we present HRQOL data from CABINET. Methods: Pts with previously treated unresectable, locally advanced or metastatic epNET or pNET were randomized (2:1) in separate cohorts to receive cabo 60 mg daily vs pbo. HRQOL was an exploratory endpoint measured using the EORTC QLQ-C30, QLQ-GI.NET21, Patient Global Impression of Change (PGIC), and PRO-CTCAE questionnaires. Optional participation was by paper surveys at baseline and every 12 weeks (wks) until disease progression or new anticancer therapy. Mean changes from baseline were compared between treatment arms at wk12 using general linear mixed models. Minimally important within-arm improvements and between-arm differences were defined as 8 points on the C30 Global Health Status (GHS)/QOL Scale. PGIC was dichotomized as improved vs unchanged/worsened and compared using Chi-squared tests. Rates of pt-reported adverse events (AEs) by PRO-CTCAE were baseline-adjusted and compared using Fisher’s exact tests. Results: 172 pts (113 cabo, 59 pbo) with epNET and 81 pts (53 cabo, 28 pbo) with pNET consented for survey participation. Pts completed 524 (82%) of 640 expected surveys across baseline, wk12, and wk24. For epNET, C30 GHS/QOL was significantly improved at wk12 in pts receiving cabo (mean change 9.5, standard error (SE) 2.2, p < 0.001) but not pbo (mean change 0.2, SE 3.1, p = 0.95) resulting in significantly different mean changes from baseline between arms (p = 0.02). For pNET, C30 QHS/QOL was significantly improved at wk12 in pts receiving cabo (mean change 8.0, SE 3.0, p = 0.008) but not pbo (mean change 6.8, SE 4.4, p = 0.12); mean changes from baseline did not statistically differ between arms (p = 0.82). No significant differences in mean changes from baseline at wk12 in C30 Physical, Role, Emotional, Cognitive and Social Function were observed between arms in the epNET or pNET cohorts. In both cohorts at wk12, pts on cabo reported improved overall status as measured by PGIC more often than those on pbo (epNET: 38% vs 19%, p = 0.04; pNET: 57% vs 18%, p = 0.006). Rates of pt-reported AEs were statistically significantly higher in cabo for diarrhea (68% vs 53%), hand-foot syndrome (57% vs 26%), mouth or throat sores (47% vs 27%), and dysgeusia (67% vs 37%) [all p < 0.05]. GI.NET21 data will be presented. Conclusions: Although cabo is associated with pt-reported AEs consistent with its known safety profile, global HRQOL was maintained. A higher proportion of patients receiving cabo reported improved overall status. Results support cabo as a treatment option for pts with previously treated advanced NET that preserves patient HRQOL. Clinical trial information: NCT03375320 .

TPS4616 Background: Osseous metastases (OM) occur in approximately 30% patients with advanced RCC. Despite therapeutic advances, OM are associated with poor survival and risk of symptomatic skeletal events (SSEs). Cabozantinib targets multiple tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors and MET (Mesenchymal-Epithelial Transition factor), which are overexpressed in OM, contributing to cabozantinib’s enhanced bone activity. Radium-223, an alpha-emitting bone-seeking radioisotope, prolongs survival in men with metastatic castration-resistant prostate cancer to the bone. Building on this therapeutic approach targeting OM, our pilot study of radium-223 with VEGF inhibition in RCC with OM has also shown safety, improvement in circulating bone turnover markers, and early efficacy (McKay et al, CCR 2018). To address the unmet need to improve SSE rates and outcomes in RCC and OM, we designed a study investigating cabozantinib with or without radium-223 in patients with RCC with OM (NCT04071223). Methods: This is an open-label, multicenter randomized phase-2 study. Key inclusion criteria include metastatic RCC of any histology with ≥1 OM, at least 1 OM without prior radiation, any number of prior therapies, and Karnofsky performance status ≥ 60%. Use of a bone protecting agent is required unless contraindicated. Patients are randomized 1:1 to cabozantinib with (Arm A) or without (Arm B) radium-223. The starting dose of cabozantinib for Arm A is 40 mg by mouth daily to be escalated to 60 mg daily after cycle 1 (1 cycle = 28 days) if no persistent grade 2 or grade ≥3 toxicity. Radium-223 is administered at a fixed dose of 1.49 microcurie/kg IV every 28 days x 6 doses. The starting dose for cabozantinib in Arm B is 60 mg daily. The primary endpoint is SSE-free survival. Secondary endpoints include safety, progression-free survival, overall survival, time to first SSE, objective response rate, time to subsequent anti-cancer therapies, quality of life (QoL) measures, and correlative analyses including liquid biopsy and tumor tissue analysis. The study is designed to have 85% power to detect an improvement in 6-month SSE-free survival rate from 65% to 78% with one-sided α = 0.05 significance. To ensure 124 evaluable patients, target accrual is 134 (67 per arm). The group-sequential design includes a safety run-in and an interim analysis for futility when 50% of the expected number of events have been observed. The safety run-in, performed in the first 12 patients randomized to combination therapy, did not demonstrate dose limiting toxicities. Final data analysis will occur when 99 events have been observed. The study was activated in July 2020 and accrual is ongoing throughout the National Clinical Trials Network (NCTN). Continued site participation and enrollment are essential to evaluate this therapeutic strategy. Clinical trial information: NCT04071223 .

4568 Background: The 2IR immune response score was initially developed using bulk RNA sequencing of pre-treatment tissue from ImVigor 210 and CheckMate 275 trials, however these trials enrolled patients (pts) with pure urothelial carcinoma (pUC) histology. Patients with hsUC often exhibit worse response to immune checkpoint inibitors (ICI) than patients with pUC. Here, we evaluated the 2IR score as a prognostic or predictive biomarker in real-world pts with hsUC. Methods: Specimens from pts with pUC (n = 1677) and hsUC (n = 417) were profiled at Caris Life Sciences (Phoenix, AZ) using next generation sequencing (NGS) of DNA and RNA. HsUC histologies included majority ( > 50%) squamous (n = 340), sarcomatoid (n = 51), neuroendocrine (n = 20), and micropapillary (n = 6) component. 2IR was calculated by comparative RNA expression of 10 adaptive immune genes and 39 pro-tumorigenic genes. Tumors were classified as 2IR-Low (2IR ≤ -0.5), -Mid (-0.5 < 2IR < 0), and -High (2IR ≥ 0), as previously described (Wang et al., 2022). Spearman correlation analysis was utilized to compare 2IR with tumor mutation burden (TMB), interferon score (IFN) and the tumor microenvironment (TME) cell fractions estimated using quanTIseq. Clinical outcomes included real-world overall survival (rwOS) from ICI start to last contact and time on treatment (ToT) with pembrolizumab, obtained via matched insurance claims data and calculated using Kaplan-Meier methods, while Hazard ratio (HR) was calculated by Cox proportional model. Results: For patients with hsUC, distribution of 2IR score was High 5.76%, Mid 33.3%, and Low 60.9%. Median 2IR score was significantly lower in squamous (-0.60, p < 0.0001) and sarcomatoid UC (-0.82, p < 0.0001) compared to pUC (-0.41) and significantly higher in neuroendocrine UC (-0.15, p = 0.003). Among patients with hsUC, median rwOS was significantly longer for patients with high/mid 2IR score compared to low 2IR score (25.3 [10.9-39.3] months vs. 8.7 [6.2-11.3] months; HR 0.52, 95% CI 0.34 – 0.78, p = 0.0017). ToT with pembrolizumab was also significantly longer for high/mid 2IR score compared to low 2IR score (3.0 [1.4-5.5] months vs. 2.1 [1.4-3.3] months; HR 0.68, 95% CI 0.46-1.00, p = 0.0471). Similar to pUC, 2IR score in patients with squamous UC was positively associated with CD8 T cell infiltration (r = 0.39; p < 0.0001), IFN score (r = 0.41, p < 0.0001), and TMB (r = 0.20, p < 0.001) and negatively associated with M1 macrophage infiltration (r = -0.25, p < 0.0001). 2IR scores in hsUC correlated positively but not significantly with mutations in TP53 (Median: -0.59 vs -0.62, p = 0.067) and PIK3CA (Median: -0.56 vs -0.61, p = 0.172) and negatively with mutations in CDKN2A (Median: -0.67 vs -0.59, p = 0.052). Conclusions: In a real-world cohort of patients with hsUC, we show the 2IR score may be prognostic for rwOS and predictive for pembrolizumab ToT. Prospective studies are needed to further validate this biomarker for use in this population.

3011 Background: BMS-986504 selectively binds to the PRMT5-MTA complex, which represents a synthetic lethal target in MTAP -del cancer cells, while sparing MTAP– wild-type cells. In the first-in-human phase 1/2 CA240-0007 study in advanced, unresectable or metastatic solid tumors with homozygous MTAP -del, BMS-986504 was found to be well tolerated and demonstrated antitumor activity in multiple tumors. Here, we report clinical results and the first PK and PD analyses of BMS-986504 from the dose escalation and expansion phases of CA240-0007. Methods: Pts with measurable/evaluable disease and no available treatment (Tx) with curative intent were enrolled; 7 doses were evaluated (50 to 800 mg) in dose escalation. Objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), safety, PK, PD, including plasma SDMA were assessed. Results: As of 2 Dec 24, 152 heavily pretreated pts were enrolled across all doses: NSCLC (n = 34), PDAC (n = 41), cholangiocarcinoma (n = 12), and mesothelioma (n = 12) were the most common tumor types. With a median f/u of 9.0 mo (95% CI 7.6–9.9), continued durable antitumor activity and deepening tumor regression were seen across tumor types and doses (ORR = 23%, DCR = 70%, median DOR = 10.5 mo, TTR = 4.6 mo). No new safety signals were identified. Most Tx-related adverse events (TRAEs) were grade (Gr) 1 or 2; 13% had Gr ≥ 3 TRAEs (Gr 3 = 12%, Gr 4 = < 1%, Gr 5 = 0). Doses from 50 to 600 mg QD were assessed for PK/PD. The AUC (0-24) after multiple doses was approximately dose proportional at 200 to 600 mg, and the terminal t 1/2 after a single dose was approximately 24 h (table). There were dose-dependent reductions in predicted plasma SDMA, with the 400 and 600 mg doses approaching the plateau. Conclusions: With longer f/u, BMS-986504 continued to show increasingly durable antitumor activity. BMS-986504 demonstrated a favorable PK/PD profile, supporting QD dosing at 400 and 600 mg. These results support further investigation of BMS-986504 at 400 and 600 mg QD as a potential first-in-class synthetic lethal Tx option in pts with advanced solid tumors with MTAP -del. Clinical trial information: NCT05245500 . PK and PD. 50 mg QD 100 mg QD 200 mg QD 400 mg QD 600 mg QD PK after multiple doses t max a (min–max), h 2.0 (2.0–4.0)n = 3 2.0 (1.0–2.0)n = 3 2.0 (0.5–6.0)n = 8 2.0 (0.5–4.0)n = 10 2.0 (1.0–6.0)n = 10 C max , b ng/mL 107n = 3 377n = 3 685n = 8 1240n = 10 2110n = 10 AUC (0-24) , b h∙ng/mL 948 n = 3 3060 n = 3 7150 n = 7 11,800n = 10 26,700n = 9 AUC (0-24) , b,c h∙ng/mL/mg 19.0n = 3 30.6n = 3 35.8n = 7 29.5n = 10 44.6n = 9 Terminal t 1/2 after single dose, d h 21.7 n = 1 80.7 n = 1 21.5 n = 14 21.7 n = 14 24.1 n = 1 PD Translational exposure targets (C avgss ), X 0.08 0.21 0.5 1.1 1.7 Predicted plasma SDMA reduction, a % (90% PI) 30.0 (23.2–37.8) 38.8 (27.1–47.5) 48.3 (42.0–53.0) 55.0 (50.7–57.6) 57.4 (54.3–59.0) a Median. b Geometric mean. c Dose-normalized. d Arithmetic mean.

ABSTRACT Trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis can prevent Pneumocystis jirovecii pneumonia (PJP) and other opportunistic infections (OI). We sought to assess the frequency, causative factors, and impact of early TMP/SMX discontinuation in abdominal solid organ transplant (SOT). This is a single‐center, retrospective cohort study of abdominal SOT recipients at Mayo Clinic Arizona (MCA) between January 2021 and June 2023. Primary study goals were to determine the rate and reasons behind early TMP/SMX discontinuation and whether TMP/SMX prophylaxis was reinitiated. Secondary outcomes included mean duration of therapy, alternative prophylactic agent utilized, and incidence of TMP/SMX‐preventable OI. A total of 930 abdominal SOT recipients were included (592 kidney, 253 liver, 85 multiorgan transplants). TMP/SMX was discontinued early in 184 (20%) patients: 77 kidney, 84 liver, 23 multiorgan. Predominant reasons for discontinuation were hyperkalemia (39%) and cytopenias (35%). Median duration of TMP/SMX prophylaxis before discontinuation was 54.5 (18.0, 93.2) days. TMP/SMX was not resumed in 62% of cases (36% kidney, 89% liver, 52% multi‐organ). The predominant reason for non‐resumption was alternative prophylaxis with no clear intent to rechallenge TMP/SMX (70%). Alternative prophylaxis included pentamidine (43%), none (30%), dapsone (22%), and atovaquone (5%). Of patients reinitiated, 86% (59/69) successfully remained on TMP/SMX through the prophylaxis period. One TMP‐SMX‐preventable OI (nocardiosis) was observed in the TMP/SMX discontinuation group. TMP/SMX is often discontinued prematurely in SOT recipients without resumption despite resolution of the offending cause. TMP/SMX prophylaxis should be maintained where possible, as alternative therapy may not offer the same broad spectrum of protection against OI.

Abstract Introduction Sleep apnea impacts 50-70% of patients following stroke. Treatment of obstructive sleep apnea (OSA) in patients with stroke using continuous positive airway pressure (CPAP) has been recommended in recent American Heart Association/American Stroke Association guidelines. However, stroke patients poorly tolerate CPAP and often remain untreated. There is a paucity of data regarding alternative treatments such as oral appliance therapy (OAT) in stroke patients. We hypothesized that oral appliance therapy would be an efficacious option in the treatment of OSA in stroke patients, defined as a ≥50% reduction in apnea-hypopnea index (AHI) or oxygen desaturation index (ODI) or reduction in total AHI or ODI to &lt; 10/h. Methods We performed a retrospective review of patients with OSA treated with OAT at our institution and had a history of stroke prior to receiving the oral appliance. Chart abstraction included demographic data, stroke type, sleep apnea diagnostic data, and efficacy data. Efficacy data included repeat sleep studies, overnight oximetry, patient reported outcomes, and subjective benefit, as available. Results 23 patients (52% female, mean age 63) were identified with a history of stroke prior to use of OAT for OSA. Baseline parameters (mean, SD) included BMI (30.8, 4.2), AHI (15.0, 10.6), and Epworth Sleepiness Scale (ESS) (9.3, 5.4). Post-treatment parameters included (mean, SD) BMI (30.1, 4.2), AHI (12.4, 12.0), and ESS (6.5, 4.0). 12 patients had both baseline and follow-up sleep studies performed which met criteria for AHI efficacy of OAT in 7 of 12 (58%). Wilcoxon signed rank exact test demonstrated improvement in median AHI of 9.3 (0.40-17.6, p&lt; 0.05) among these 12 patients. 2 of 3 (67%) patients with overnight oximetry follow-up met criteria for ODI efficacy of OAT. Of 8 patients with only subjective follow-up, 6 (75%) reported subjective improvement and 2 (25%) did not tolerate the device. Conclusion This study demonstrated that oral appliance therapy is efficacious in reducing the AHI by at least 50% or to a value below 10 in a majority of patients. Oral appliance therapy may be a viable alternative to CPAP in selected OSA patients with a history of stroke. Support (if any) No support

Précis: Using a CNN-enhanced platform, 60-4 visual fields identified peripheral glaucomatous defects missed by central testing in mild cases; facial contour correction showed these defects occurred exclusively outside the temporal visual field. Purpose: To develop a methodology to separate facial contour-induced visual field defects from defects related to glaucoma in patients with peripheral field defects. Methods: Ninety-seven eyes from 50 patients previously diagnosed with glaucoma were enrolled in the study. Thirty-one (62%) participants were male, and 86% were white. The study involved patients with glaucoma who underwent visual field testing using standard automated perimetry, including 10-2, 24-2, 30-2, and 60-4 visual fields. A convolutional neural network (CNN)-enhanced platform, previously developed to identify facial contour-dependent defects in healthy subjects, was used to analyze the visual field data. Patients: The study included 97 eyes from 50 patients with glaucoma, with the majority having primary open angle glaucoma. Results: In 90 out of 97 eyes, there were 60-4 visual field defects. However, 20 (22%) of these eyes did not have glaucomatous defects on the 10-2 or 30-2 visual fields. All patients with 60-4 defects in the absence of more central defects had mild glaucoma, and these eyes comprised 38% of the mild glaucoma group. 60-4 visual field increased the sensitivity of identifying glaucoma in mild disease. Without facial contour, the 60-4 visual field mean threshold summation was 1099.6±346.6 dB, and decreased to 1057±331 dB when accounting for facial contour, which affected 8.03%±4.02% of test points. Facial contour-dependent visual field defects were exclusively found outside the temporal visual field. Conclusion: The study demonstrated the potential utility of 60-4 visual fields for identifying early functional glaucomatous changes that may not be detected by more central visual field tests (10-2 or 30-2). It may be important to consider peripheral visual field defects, which can be affected by facial contour, in the diagnosis and monitoring of glaucoma, particularly in mild cases.

Abstract Introduction: Non-Cystic Fibrosis Bronchiectasis (NCFB) is an obstructive pulmonary disease associated with structural lung disease, altered mucociliary clearance, hyper mucus secretion, recurrent infection, and airway inflammation that results in significant morbidity and mortality. Aspergillus sp (Asp) is a common fungi isolated in respiratory specimens of those with lung disease and is associated with both infectious and allergic pulmonary diseases such as Asthma and Cystic Fibrosis. Despite individuals with NCFB having similar phenotypes as these conditions, the impact of Asp on this population is poorly understood. Methods: We performed a cross-sectional retrospective analysis from the US Bronchiectasis and NTM Research Registry (BRR). NCFB patients without a history of lung transplant who had at least one respiratory Asp culture were included. We compared patients with no history of Asp grown from respiratory culture to those with at least one positive respiratory culture for Asp during the available period. Patient demographics, bacterial culture history, lung function, comorbidities, modified Bronchiectasis Severity Index (mBSI), and sputum parameters were analyzed descriptively. Comparisons between groups were conducted using Kruskal-Wallis, independent sample t-tests, and chi-square tests for continuous and categorical variables as appropriate. Results: 3985 people with NCFB met inclusion criteria. 3359 (84.3%) individuals were Asp culture negative compared to 626 (15.7%) individuals with Asp. There were notable differences in race, showing higher proportions of non-Hispanic white (90.4 vs 82.2%) in this population. While the frequency of Chronic Obstructive Pulmonary Disease and Primary Ciliary Dyskinesia were similar, there were more individuals with Asthma (31.3 vs 24.7%, p&lt;0.001) and Allergic Bronchopulmonary Aspergillosis (ABPA) (6.4 vs 2.4%, p&lt;0.001) in the Asp positive group (Figure 1A). The Asp positive group had higher blood eosinophils (150.0 vs 124.0 cells/uL, p=0.026, Figure 1B), had nominally lower lung function (73.5 vs 75.3% ppFEV1, p=0.089), and were more likely to have at least one or more positive bacterial cultures (62.9 vs 51.9%, p&lt;0.001, Figure 1C). There was no significant difference in sex, age, exacerbations, Pseudomonas aeruginosa or NTM positive cultures, sputum volume, or mBSI. Conclusion: Individuals with NCFB and history of one or more positive Asp cultures were more likely to be non-Hispanic white, have a diagnosis of Asthma and/or ABPA, higher blood eosinophils, and more positive airway bacterial cultures. Further work is needed to better understand how Asp contributes to bronchiectasis progression. More expansive analysis and multivariant modeling is underway to better understand the impact of Asp in people with NCFB.

ABSTRACT Lung cancer is the leading cause of cancer-related deaths worldwide and, despite treatment advances, immune suppression remains an obstacle to effective therapy. Effector CD4 + T cells (CD4 + Teffs) are critical for antitumor immunity, but their function is often inhibited by regulatory T cells (Tregs), which accumulate in lung tumors and perform suppressive functions through multiple mechanisms. This suppression leads to tumor progression and poor patient outcomes. However, the mechanisms underlying Treg-mediated suppression are not fully understood. Here, we identify the extracellular ATP receptor P2RX7 as a key regulator of Treg function in lung tumors. Using a murine lung cancer model induced by Lewis lung carcinoma cells, we demonstrate that P2RX7 enhances the suppressive capacity of tumor-infiltrating Tregs, promoting tumor growth. In T cell-specific P2RX7-KO mice, reduced Treg infiltration was accompanied by increased CD4 + Teff accumulation and improved tumor control. Treg-specific P2RX7-KO mice exhibit reduced tumor growth, confirming a cell-intrinsic role of P2RX7 in Tregs. Suppression assays revealed that tumor-infiltrating WT Tregs have greater suppressive activity compared to P2RX7-KO Tregs, which failed to inhibit type 1 and Tfh-like responses. This was associated with increased tumor-specific IgG production by lung B cells in P2RX7-KO mice. We also observed that WT Tregs express higher levels of the immunosuppressive surface molecule CTLA-4 when compared to P2RX7-KO Tregs. In summary, we show that P2RX7 expression on Tregs is essential for their suppressive function in lung cancer, and targeting of P2RX7 may constitute a novel strategy to improve lung cancer treatment by alleviating Treg-mediated immune suppression.