Immunotherapy Studies Research Articles

Identifying putative allergens from Cenostigma pluviosum pollen using proteomic bioinformatics.

Routinely, signs and symptoms of pollinosis worsen during the flowering period of the Cenostigma pluviosum var. peltophoroides (Sibipiruna) trees. This study aimed to determine whether Sibipiruna pollen contains allergenic proteins. The pollen from mature Sibipiruna anthers was morphologically characterized using optical, scanning electron and emission microscopy. Additionally, biochemical characterization was conducted through Shotgun Label-Free Proteomic Analysis. Three hundred and forty-nine proteins were identified using the UNIPROT database and thirty-six were confirmed as homologous allergenic proteins in the Allergome database. At the first time, Sibipiruna pollen allergenic proteins have been described and this study provides a deeper understanding of the allergenic proteins present in this pollen. These preliminary findings can be useful to assist in the development of targeted extracts for the study of sensitization and potential immunotherapy in the future.

NIMG-51. PROSPECTIVE CASE CONTROL STUDY OF HYPOXIA FMISO PET/MRI AS A DIAGNOSTIC FEATURE OF GLIOBLASTOMA IMMUNOTHERAPY FAILURE

Abstract BACKGROUND Hypoxia is a prognostic biological feature of glioblastoma. 18F-fluoromisonidazole (FMISO) PET quantifies tumor hypoxia. Efficacy of checkpoint immunotherapy is being investigated, but specific response assessment criteria remain unknown. We hypothesized that tumor hypoxia is a defining feature of immunotherapy failure in patients with glioblastoma. METHODS A prospective case control study was undertaken in patients with newly diagnosed IDH wildtype glioblastoma (NCT03649880). Cases were concurrently enrolled in a phase II study (NCT03347617) of pembrolizumab immunotherapy (200 mg IV every 3 weeks) combined with Stupp protocol temozolomide-based chemoradiotherapy following maximal safe resection. Controls did not receive pembrolizumab. FMISO PET/MRI (3.7 MBq/kg, 90 min uptake) was performed at time of mRANO presumed progression. Hypoxic volume (HV) was defined by pixels with FMISO uptake ≥1.2x that of mean cerebellar uptake. MRI-Gd enhancing volume was segmented using a semi-automated approach. Hypoxic fraction (HF) was defined as the HV-to-MRI enhancing volume ratio. Disease progression or pseudoprogression (Psp) was confirmed through surgery or follow-up MRI. T-test and receiver operator characteristic (ROC) analysis assessed differences and diagnostic performance. RESULTS 18 patients (14 cases [11 progression and 3 Psp] and 4 controls [3 progression and 1 Psp]) provided evaluable disease. For all patients, HF was significantly elevated with progression (1.44 ± 0.8; N=14) compared to Psp (0.31 ± 0.3; N= 4; P=0.01). HV was not different (P=0.10). No difference in HV or HF was observed between Cases and Controls (P> 0.42). Use of HF yielded an AUROC of 0.96 with an optimal cut off of 0.74, to differentiate progression from Psp. CONCLUSION At mRANO presumed progression HF with FMISO PET/MRI accurately distinguishes tumor progression from neuroinflammatory Psp, irrespective of prior pembrolizumab immunotherapy. The incorporation of FMISO PET/MRI in larger prospective therapeutic clinical trials in patients with glioblastoma is underway and likely to improve response assessment criteria.

TMOD-08. DETAILED GENERATION OF AN ORTHOTOPIC INTRACRANIAL GLIOBLASTOMA (GBM) PATIENT-DERIVED XENOGRAFT (PDX) MODEL FOR PRECLINICAL IMMUNOTHERAPEUTIC STUDIES

Abstract PURPOSE This study aimed to establish an orthotopic intracranial PDX mouse model using cryopreserved GBM tissues expanded in a heterotopic subcutaneous PDX model for immunotherapeutic studies. The model is designed to closely replicate human GBM, enabling the exploration of its pathophysiology and the development of effective immunotherapies for this type of cancer. METHODS Glioblastoma tissues from 16 fresh and cryopreserved samples were used to establish a heterotopic subcutaneous PDX mouse model for tumor expansion. Successful engraftments were then used to create an orthotopic intracranial PDX mouse model. The tumor formation rates and durations were estimated in both models. Tumor fidelity to the original GBM tumors was confirmed through immunohistology (GFAP, P53, and Ki67) and genetic analysis (whole exome sequencing, RNA sequencing, and methylome analysis). The therapeutic effects of immunotherapy (allogenic NK cells) in combination with Avastin and Irinotecan were tested in the orthotopic intracranial PDX model. RESULTS The orthotopic intracranial GBM mouse model achieved 100% engraftment from successful tumor growth in the subcutaneous PDX model. The overall success rate was 81.25% (85.71% for cryopreserved tissues), with a median process duration of 26.5 weeks (19 weeks for the subcutaneous and 7.5 weeks for intracranial establishment). No significant differences in tumor formation were observed within one year for cryopreserved tissue in the subcutaneous model. Molecular and genetic analysis confirmed similar tumor characteristics between the intracranial PDX tumors and the original patient tumors. Additionally, NK cells combined with Avastin and Irinotecan demonstrated efficacy in this model. CONCLUSIONS We successfully established an orthotopic intracranial PDX mouse model using cryopreserved GBM tissues, with no observed differences within one year. These models accurately mirror patients’ tumor characteristics, promising advancements in glioblastoma research and treatment, particularly for immunotherapy studies. Keywords: Glioblastoma (GBM), cryopreserved GBM tissues, patient-derived xenograft (PDX) model, NOD/SCID IL-12Rγnull (NSG) mice

Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread.

The transmission of tau pathology has been proposed as one of the major mechanisms for the spatiotemporal spreading of tau pathology in neurodegenerative diseases. Over the last decade, studies have demonstrated that targeting total or pathological tau using tau antibodies can mitigate the development of tau pathology in tauopathy or Alzheimer's disease (AD) mouse models, and multiple tau immunotherapy agents have progressed to clinical trials. Tau antibodies are believed to inhibit the internalization of pathologic seeds and/or block seed elongation after seed internalization. To further address the mechanism of tau antibody inhibition of pathological spread, we conducted immunotherapy studies in mouse primary neurons and wild-type mice (females) seeded with AD patient-derived tau to induce the formation and spreading of tau pathology. Notably, we evaluated the effect of a mouse tau-specific antibody (mTau8) which does not interact with AD-tau seeds in these models. Our results show that mTau8 crosses the blood-brain barrier at levels similar to other antibodies and effectively decreases AD-tau-seeded tau pathology in vitro and in vivo. Importantly, our data suggest that mTau8 binds to endogenous intraneuronal mouse tau, thereby inhibiting the elongation of internalized tau seeds. These findings provide valuable insights into the possible mechanism underlying antibody-based therapies for treating tauopathies.Significance Statement The transmission of tau pathology plays key role in the pathoclinical progression of tauopathy. Studies have shown that tau antibody treatment can mitigate tau pathology in transgenic and spreading models of tauopathy. To explore the mechanisms involved in this procedure, we conducted immunotherapy studies on human tau seeds induced tau spreading models using a mouse tau-specific antibody (mTau8), which does not interact with human-tau seeds. Our findings in the study enhance our understanding of antibody-based therapies for tauopathies.

Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.

Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM. An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies. NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice. NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.

Perioperative Tislelizumab plus intensity modulated radiotherapy in resectable hepatocellular carcinoma with macrovascular invasion: a phase II trial

Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) have dismal prognosis and there are no standard perioperative therapies. This phase 2 trial (ChiCTR2000036385) aimed to investigate the activity and safety of perioperative tislelizumab plus intensity modulated radiotherapy (IMRT) for resectable HCC with MVI. Thirty treatment-naïve patients with MVI received 3 cycles of tislelizumab intravenously (200 mg, every three weeks) and concurrent IMRT (45 Gray in 15 fractions). Primary endpoints were the overall response rate (ORR) and overall survival (OS). Secondary endpoints were the proportion of patients with a complete or major pathological response (pCR or MPR), recurrence-free survival (RFS) and safety. Of patients enrolled, 15 (50%) underwent curative surgery followed by adjuvant tislelizumab. The ORR was 30.0% (90% CI 16.6%-46.5%) and the median OS was 18.7 months. Of the 15 patients underwent surgical resection, 10 (66.7%) achieved pCR or MPR and 8 (53.3%) remained recurrence-free. The median RFS were not reached with a median follow-up of 21.77 months (95% CI 12.50-31.03) post-surgery. 4 (13.3%) patients experienced grade 3 treatment-related adverse events. The most common events were thrombocytopenia, leukopenia, and anemia. The trial has met the pre-specified endpoints, and these results support further studies of perioperative immunotherapy plus radiotherapy in HCC.

Association of immunoglobulin E levels with glioma risk and survival.

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free controls (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Elevated total IgE was associated with reduced risk of IDH-wildtype (RR = 0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR = 0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR = 0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR = 0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.

Abstract A020: The highly predictive 3D Cell Co-Culture Model for Immunotherapy studies

Abstract A020: The highly predictive 3D Cell Co-Culture Model for Immunotherapy studies

Evaluation of Radiation Pneumonitis in a Phase 2 Study of Consolidation Immunotherapy With Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiation Therapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer

Purpose/Objective(s)The addition of immunotherapy (IO) after concurrent chemoradiation (CCRT) for unresectable non-small cell lung cancer (NSCLC) has become common practice in eligible patients. Approaches to further improve outcomes and reduce treatment-related toxicity for these patients are needed. This study evaluates the risk of radiation pneumonitis after CCRT and its correlation with the radiation dose distribution, immunotherapy regimen (nivolumab vs nivolumab plus ipilimumab), and patient demographics across BTCRC-LUN16-081. Materials/MethodsPatients with unresectable stage III NSCLC after completion of CCRT were enrolled on BTCRC-LUN16-081, a randomized phase II trial to assess efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for six months. Radiation dose parameters, patient demographics, and toxicity events were evaluated among treatment arms for risk and severity of pneumonitis. ResultsOne-hundred and five patients were enrolled into two treatment arms, 54 patients received nivolumab alone and 51 patients received nivolumab plus ipilimumab. Of these, 104 patients had dose volume histogram (DVH) information available. Within this cohort, 65 patients (62.5%) had stage IIIA and 39 patients (37.5%) had stage IIIB NSCLC disease per AJCC 7th edition. During the study, 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. Utilizing logistic regression and evaluating different cut-offs for lung V20, patients with V20 >23% demonstrated significantly higher grade 2 or greater pneumonitis rates (37.1% vs. 16.2%, P = .031). No significant difference in rates of pneumonitis between arms were identified. Traditional lung DVH cut-offs (V5 of >65%, V20 of >35%, mean >20 Gy) were not associated with pneumonitis. ConclusionIn patients receiving nivolumab or nivolumab plus ipilimumab after definitive CCRT, lung V20 of >23% was associated with an increased risk of grade 2 or greater pneumonitis. Radiation dose constraints for lungs in patients receiving consolidative IO after CCRT should continue to be evaluated and optimized when feasible.

Mechanistic studies of tumor-associated macrophage immunotherapy.

Tumor-associated macrophages (TAMs) are present in the tumor microenvironment and can polarize into subtypes with different functions and characteristics in response to different stimuli, classifying them into anti-tumorigenic M1-type and pro-tumorigenic M2-type. The M1-type macrophages inhibit tumor growth through the release of pro-inflammatory cytokines, whereas the M2-type macrophages contribute to tumor progression through the promotion of tumor proliferation, angiogenesis and metastasis. Due to the duality of macrophage effects on tumors, TAMs have been a hot topic in tumor research. In this paper, the heterogeneity and plasticity of TAMs, the interactions between TAMs and other immune cells, and the effects of TAMs on tumors are reviewed, and the therapeutic strategies for TAMs are summarized and discussed. These therapeutic strategies encompass methods and approaches to inhibit the recruitment of TAMs, deplete TAMs, and modulate the polarization of TAMs. These studies help to deeply understand the mechanism of TAMs-tumor interaction and provide reference for combination therapy of tumors.

Research Progress on Dendritic Cells in Hepatocellular Carcinoma Immune Microenvironments.

Dendritic cells (DCs) are antigen-presenting cells that play a crucial role in initiating immune responses by cross-presenting relevant antigens to initial T cells. The activation of DCs is a crucial step in inducing anti-tumor immunity. Upon recognition and uptake of tumor antigens, activated DCs present these antigens to naive T cells, thereby stimulating T cell-mediated immune responses and enhancing their ability to attack tumors. It is particularly noted that DCs are able to cross-present foreign antigens to major histocompatibility complex class I (MHC-I) molecules, prompting CD8+ T cells to proliferate and differentiate into cytotoxic T cells. In the malignant progression of hepatocellular carcinoma (HCC), the inactivation of DCs plays an important role, and the activation of DCs is particularly important in anti-HCC immunotherapy. In this review, we summarize the mechanisms of DCs activation in HCC, the involved regulatory factors and strategies to activate DCs in HCC immunotherapy. It provides a basis for the study of HCC immunotherapy through DCs activation.

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

An Integrated Immune-Related Bioinformatics Analysis in Lung Squamous Cell Carcinoma Patients

Through combined bioinformatics analysis, the goal of untrrec research was to develop and confirm the immune-related prognostic signature in LUSC (lung squamous cell carcinoma). We constructed an optimized prognostic risk model consisting of five PIR-lncRNAs (AC107884.1, LCMT1-AS1, AL163051.1, AC005730.3 and LINC02635). To evaluate and verify the prognostic value of the model, we subsequently conducted independent prognostic and mortality analysis on the prognostic risk model. Additionally, we conducted a distinct study of immune cell infiltration in the model among high- and low individuals. By using co-expression network analysis, we were able to identify 654 immune-related lncRNAs (IR-lncRNAs) and 18 prognostic IR-lncRNAs (PIR-lncRNAs) and derive 546 differently expressed genes and 21 immune-related genes. We proved that the impact of immunotherapy in individuals in the high-risk category may be lessened through the study of immune escape and immunotherapy. Our findings elucidate the intrinsic molecular biological link between the pathogenic genes of LUSC and immune cells, which has important exploration and reference significance for the precise and potential immunotherapy of LUSC patients, especially for high-risk patients.

319TiP NeoBREASTIM: A phase II study of atezolizumab plus RP1 oncolytic immunotherapy in the neoadjuvant setting of triple-negative breast cancer (TNBC)

319TiP NeoBREASTIM: A phase II study of atezolizumab plus RP1 oncolytic immunotherapy in the neoadjuvant setting of triple-negative breast cancer (TNBC)

New Metabolomic Insights Into Cancer.

Cancer has been marked by metabolic irregularities that fuel various aggressive activities such as rapid cell proliferation, evasion of the immune system, and spread to distant organs. Therefore, exploiting cancer metabolism for diagnosis, monitoring, or treatment has been extensively studied in the past couple of decades with various molecular and cellular techniques. More recently, investigating cancer diagnostics and treatments through advanced metabolomics has emerged, and these comprehensive approaches provide a holistic understanding of cancer metabolism, which supported the discovery of metabolic targets relevant across multiple cancer types and the development of more effective treatments. This study offers highlights of new knowledge on cancer metabolism enabled by recent metabolomics studies and their potential applications in aiding cancer research and predicting cancer treatment outcomes. Specifically, we discussed the use of advanced metabolomics in cancer metabolism, tumor microenvironment, and cancer immunotherapy studies to provide valuable insights that can shape future research efforts in the dynamic field of cancer metabolism research.

TGFβ in malignant canine mammary tumors: relation with angiogenesis, immunologic markers and prognostic role

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.

Bioprinting of tumor immune microenvironment for immunotherapy

Accurately simulating the tumor immune microenvironment (TIME), which consists of a tumor, extracellular matrix (ECM), vascular network, and a variety of stromal and immune cells, is crucial for advancing and testing immunotherapies such as checkpoint inhibitors, chimeric antigen receptor-T (CAR-T) cells, and cancer vaccines. Traditional models, such as animal models, are limited by their differences from human immune environments. Bioprinting addresses these limitations by incorporating tumors, immune cells, and vascular cells within an ECM, thereby reflecting the complex interactions, including trafficking, between cancer and immune cells. These models provide better predictive accuracy for human immune responses, reducing translational failures and improving preclinical testing. While bioprinting methods for simulating the tumor microenvironment, where cancer cells form spheroids surrounded by blood vessels, are well reviewed, bioprinting methods for recapitulating the TIME are not as thoroughly explored. This review aims to fill this gap by exploring the development, application, and potential of bioprinted TIME models in enhancing the study and efficacy of immunotherapies, ultimately offering a more realistic and personalized approach to cancer treatment. &amp;nbsp;

Multi-Drug Resistance and Breast Cancer Progression via Toll-Like Receptors (TLRs) Signaling.

Toll-like receptors (TLRs) are essential receptors involved in inflammation and innate immunity. Various types of cancer cells, as well as innate immune cells, express TLRs. There is mounting proof that TLRs are critical to the development and spread of cancer as well as metabolism. In breast cancer, up-regulated levels of TLRs have been linked to the aggressiveness of the diseases, worse treatment outcomes, and the emergence of therapeutic resistance. Patients with advanced non-resectable, recurring, and metastatic breast cancer currently have few available treatment choices. An intriguing new strategy is an innate immunity-mediated anticancer immunotherapy, either used alone or in conjunction with existing treatments. In fact, several TLR agonists and antagonists have been used in clinical studies for anti-cancer immunotherapy. Consequently, TLRs serve as critical targets for controlling the course of breast cancer and treatment resistance in addition to being implicated in immune responses against pathogen infection and cancer immunology. In this review, we deliver an overview of the most current findings on TLR involvement in the development of breast cancer and treatment resistance.

Muscle-invasive and metastatic urothelial carcinoma of the urinary bladder : Current state of histopathologic, molecular, and immunologic prognostic and predictive factors

Muscle-invasive and metastatic urothelial carcinoma (UC) represents aheterogeneous disease entity with numerous morphological, molecular, and immunological phenotypes. This article aims to provide an overview of current histopathological, molecular, and immunological prognostic and predictive factors in muscle-invasive and metastatic UC. Muscle-invasive and metastatic UC exhibits awide range of divergent differentiations and histological subtypes. The correct diagnosis of these morphological variants is essential, as they may determine the clinical course and may also present specific and potentially therapeutically targetable molecular alterations (e.g., HER2 alterations in micropapillary UC). The morphological subtypes largely correlate with the six molecular consensus subtypes. Furthermore, morphological and molecular subtypes are associated with immunological properties that are relevant for modern immunotherapies, such as the PD-L1 status. Numerous immunotherapy studies in the setting of curatively treatable muscle-invasive UC will be reported in 2024 and 2025, likely leading to an increasing number of PD-L1 testing indications.

Lessons from Post-Immunotherapy Tumor Tissues in Clinical Trials: How Can We Fuel the Tumor Microenvironment in Gliomas?

Despite recent advancements in cancer immunotherapy, many patients with gliomas and glioblastomas have yet to experience substantial therapeutic benefits. Modulating the tumor microenvironment (TME) of gliomas, which is typically "cold", is crucial for improving treatment outcomes. Clinical tumor specimens obtained post-immunotherapy provide invaluable insights. However, access to such post-immunotherapy samples remains limited, even in clinical trials, as tumor tissues are often collected only at tumor relapse. Recent studies of neoadjuvant immunotherapy provided important insights by incorporating surgical resections of post-treatment tumors. Moreover, pre-surgical immunotherapies are increasingly integrated into clinical trial designs to evaluate treatment efficacy. These investigations reveal critical information, particularly regarding the delivery success of therapeutic agents, the expansion and persistence of immune products, and the cellular and molecular changes induced in the TME. In this review, we assess the findings on post-treatment tumor specimens obtained from recent immunotherapy clinical trials on gliomas, highlight the importance of these samples for understanding therapeutic impacts, and discuss proactive investigation approaches for future clinical trials.