Dudek, Arkadiusz Z

Background. The use of immune checkpoint inhibitors (ICIs) in kidney transplant recipients (KTR) for cancer treatment is limited by concerns of allograft rejection and uncertain oncologic efficacy. Methods. We conducted a single-center retrospective study of KTR with unresectable or metastatic malignancies treated between 2018 and 2025. The primary study cohort included 33 patients treated with ICI, whose outcomes were compared with 20 matched KTR treated with non-ICI systemic chemotherapy (SC). Results. KTR treated with ICI achieved an objective response rate of 36.4% (12/33) versus 30.0% (6/20) with SC, and a clinical benefit rate of 54.5% (18/33) versus 35.0% (7/20); neither difference was statistically significant (objective response rate P = 0.77; clinical benefit rate P = 0.27). Disease progression occurred in 81.8% of ICI-treated patients and 95.0% of SC-treated patients ( P = 0.23), and death because of cancer progression occurred in 63.6% and 75.0%, respectively ( P = 0.58). Median progression-free survival was 7.3 mo (95% confidence interval [CI], 4.3-10.8 mo) in the ICI group versus 4.1 mo (95% CI, 2.8-6.3 mo) in the SC group (log-rank P = 0.156). Median overall survival was 15.1 mo (95% CI, 7.6-37.3 mo) with ICI versus 8.7 mo (95% CI, 4.9-14.8 mo) with SC (log-rank P = 0.079). Posttreatment allograft rejection occurred in 12.1% of ICI-treated patients and 0.0% of SC-treated patients ( P = 0.29), with irreversible graft loss in 3.0%. Grade ≥2 immune-related adverse events occurred in 12.1% of ICI-treated patients, and no treatment-related deaths were observed. Conclusions. ICI therapy was associated with a trend toward longer overall survival when compared with SC and with a low rate of rejection and allograft loss.

Background/Objectives: Tumor-infiltrating lymphocyte (TIL) therapy is an important option for patients with metastatic melanoma progressing after standard systemic therapy, but real-world data on treatment delivery, toxicity monitoring, and immune recovery remain limited. We evaluated clinical outcomes, treatment tolerance, immune reconstitution, and cardiac biomarker dynamics across three Mayo Clinic sites. Methods: We retrospectively analyzed adults with metastatic melanoma who received lymphodepleting chemotherapy followed by TIL infusion and high-dose interleukin-2 (IL-2) between April 2024 and December 2025. Clinical outcomes, treatment delivery, and adverse events were assessed. Longitudinal immune monitoring included CD4 and CD8 T-cell counts, CD4:CD8 ratio, and immunoglobulin G (IgG) at baseline and follow-up. In a prespecified cardiac sub-cohort, high-sensitivity troponin (hs-Tn) was measured during IL-2 administration to evaluate associations with cardiac events and IL-2 interruption. Results: Thirty-six patients underwent TIL infusion. The objective response rate was 50.0%, including complete responses in 13.9%, and the disease control rate was 72.2%. Median progression-free survival was 3.61 months, and median overall survival was 12.94 months. M1d disease was associated with inferior overall survival on univariable analysis (HR 6.55, 95% CI 2.03–21.17; p = 0.002), with attenuation after multivariable adjustment. Receipt of ≥3 IL-2 doses was associated with longer overall survival on univariable analysis (HR 0.20, 95% CI 0.06–0.64; p = 0.007), but this association also attenuated after adjustment. Longitudinal immune monitoring demonstrated persistent CD4 lymphopenia through 6 months, sustained inversion of the CD4:CD8 ratio, and declining IgG at months 3 and 6. In the cardiac sub-cohort (24 patients; 87 IL-2 doses), post-dose hs-Tn ≥15 ng/L was associated with clinically significant cardiac events (OR 9.6, 95% CI 1.5–60.6; p = 0.016) and IL-2 interruption (OR 3.4, 95% CI 1.1–10.7; p = 0.036). For cardiac events, hs-Tn ≥15 ng/L had 100% sensitivity and 100% negative predictive value. Conclusions: In routine practice, TIL therapy was feasible and active in metastatic melanoma. M1d disease identified a subgroup with poor survival, peri-dose hs-Tn showed promise as a tool to support safer IL-2 delivery, and prolonged CD4 suppression with IgG decline suggests that recovery after TIL therapy extends beyond initial hematologic reconstitution. These findings support prospective validation of biomarker-guided IL-2 monitoring and extended post-treatment immune surveillance.

Tumour-infiltrating lymphocyte (TIL) therapy has emerged as a promising adoptive cell transfer strategy for solid tumours. The recent accelerated approval of lifileucel by the Food and Drug Administration marks a significant milestone in the clinical application of TIL therapy. This review comprehensively examines the historical development, biology, clinical efficacy, safety and limitations of TIL therapy. We explore advancements in TIL manufacturing, including novel culture techniques, genetic modifications and automation, to enhance scalability and effectiveness. Despite promising results, TIL therapy faces challenges such as high-dose interleukin-2 toxicity, complex manufacturing processes and immune evasion mechanisms. Emerging strategies, including checkpoint inhibitor combinations, engineered TIL constructs and metabolic reprogramming, aim to improve TIL therapeutic efficacy. This review provides insights into the evolving landscape of TIL therapy and its potential to enhance current cancer immunotherapy.

Abstract The Phase 2 IMPRIME 1 study evaluated the combination of the pathogen-associated molecular pattern (PAMP) Imprime with the immune checkpoint inhibitor (ICI) pembrolizumab as second or later line of treatment (2 L+) for patients with metastatic triple-negative breast cancer (mTNBC). Eligible patients with mTNBC received weekly Imprime (4 mg/kg) intravenously in combination with pembrolizumab (200 mg every 3 weeks). Primary endpoints were overall response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression free survival (PFS), and overall survival (OS). Exploratory endpoints included correlations between immune cell activation markers in tumor tissues and blood and response to therapy. Of the 42 evaluable patients, six had a response (one complete, five partial), with an ORR of 14.3% by RECIST v1.1. Median PFS was 2.7 months, median OS was 16.4 months, and DCR was 54.8%, with responders achieving a median DoR of 15.2 months. Therapy was generally well tolerated and resulted in an increase of immune activation markers, with higher levels of activation in peripheral blood associated with response and improved survival. The combination of Imprime and pembrolizumab was safe and demonstrated immune activation in tumor tissues and peripheral blood in patients with TNBC. Improved response rates were observed compared to historical studies of ICI monotherapy in similar patient populations. Study number (ClinicalTrials.gov trial registration): NCT02981303.

e18634 Background: Informed patients have better health outcomes. In a study of 1,057 patient encounters with 3,552 clinical decisions, only 9% resulted in informed medical decisions.The complexity of treatments and patients' limitations in health literacy (especially common in underserved communities) make it difficult for patients to engage in SDM. In 2017, A Breath of Hope Lung Foundation introduced An Animated Patient’s Guide to Lung Cancer (APG), an online resource aimed at improving patient knowledge. Methods: APG consists of animations, expert FAQ videos, slide shows, infographics, patient-experience videos, knowledge-assessment tools, and learner feedback. Video views, duration of use, and learner responses to multiple-choice questions on the APG website were collected for 33 months – through August 2020. Total APG views, most frequently viewed animations and expert videos were monitored on the website and on YouTube, to measure learner responses to outcome-based questions, and learner intent-to-implement changes. Results: 212,336 total views: 142,998 unique visitors: 59% from U.S. and 41% from 50 other countries. Unique U.S. visitors: 43,872 patients, 16,030 caregivers, and 7,593 health providers. 94% reported they will ‘use new information to better self-manage their lung cancer’ (n = 277); 98% ‘will discuss information learned with their doctor’ (n = 455), and 93% ‘plan to discuss treatment options with their doctor’ (n = 272). Conclusions: Multimedia ‘animated’ formats of learning tailored to the needs and learning styles of lung cancer patients provides effective learning, informed patients, increased management skills, and improved engagement in shared decision making.

Abstract Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively active mutant form of EGFR that is expressed in 40% to 50% of gliomas and several other malignancies. Here, we describe the therapeutic effects of silencing EGFRvIII on glioma cell lines in vitro and in vivo. A small interfering RNA molecule against EGFRvIII was introduced into EGFRvIII-expressing glioma cells (U87Δ) by electroporation resulting in complete inhibition of expression of EGFRvIII as early as 48 h post-treatment. During EGFRvIII silencing, a decrease in the proliferation and invasiveness of U87Δ cells was accompanied by an increase in apoptosis (P < 0.05). Notably, EGFRvIII silencing inhibited the signal transduction machinery downstream of EGFRvIII as evidenced by decreases in the activated levels of Ras and extracellular signal-regulated kinase. A lentivirus capable of expressing anti-EGFRvIII short hairpin RNA was also able to achieve progressive silencing of EGFRvIII in U87Δ cells in addition to inhibiting cell proliferation, invasiveness, and colony formation in a significant manner (P < 0.05). Silencing EGFRvIII in U87Δ cultures with this virus reduced the expression of factors involved in epithelial-mesenchymal transition including N-cadherin, β-catenin, Snail, Slug, and paxillin but not E-cadherin. The anti-EGFRvIII lentivirus also affected the cell cycle progression of U87Δ cells with a decrease in G1 and increase in S and G2 fractions. In an in vivo model, tumor growth was completely inhibited in severe combined immunodeficient mice (n = 10) injected s.c. with U87Δ cells treated with the anti-EGFRvIII lentivirus (P = 0.005). We conclude that gene specific silencing of EGFRvIII is a promising strategy for treating cancers that contain this mutated receptor. [Mol Cancer Ther 2008;7(11):3586–97]