Immunotherapy Studies Research Articles

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 II Study of Consolidation Immunotherapy with Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer (NSCLC): Big Ten Cancer Research Consortium BTCRC-LUN16-081

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.

New opportunities and challenges of anal preservation strategies for rectal cancer in the era of immunotherapy

With the advancement of medical technology and concept, rectal cancer treatment methods continue to develop, further improving the efficacy of comprehensive treatment and quality of life for patients. Innovation in various anal preservation operations for low rectal cancer has continuously improved the rate of anal preservation, and the concept of the "watch and wait" strategy may become a new milestone in the treatment of rectal cancer. With the application of immunotherapy to all aspects of cancer treatment, it will certainly have a profound impact on the treatment of colorectal cancer, especially the anal preservation strategy. Combined with the new characteristics, advantages, and achievements of immunotherapy, more patients with rectal cancer can achieve the purpose of preserving the anus and organs through nonsurgical therapy, and obtain the same disease-free survival and overall survival while improving the quality of life. Currently, the study of sensitization immunotherapy for different types of bowel cancer is in the ascendancy, and the development of a better treatment plan is an urgent problem to be explored and solved.

Reshaping tumor microenvironment by regulating local cytokines expression with a portable smart blue-light controlled device

Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.

Effect of SBRT plus immunotherapy on immune status and survival quality of NSCLC patients: A study of combined radiotherapy and immunotherapy.

non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer populations. Stereotactic radiotherapy (SBRT) is mainly suitable for early NSCLC patients who are not suitable for surgery or refuse surgery. To analyze the effects of stereotactic radiotherapy (SBRT) plus immunotherapy for non-small cell lung cancer (NSCLC) patients on their immune status and survival quality. NSCLC patients admitted to our hospital from 2019-2022 were divided into 61 cases in control group (SBRT) and 60 cases in observation group (SBRT plus immunotherapy) by the randomized numerical table method to compare the efficacy, the level of tumor markers in the serum, the level and activity of the immune cells in the peripheral blood and the Kahlil's functional status (KPS) scores. The observation group had a higher efficacy rate than that of the control group (P< 0.05). There was no statistical difference between the two groups in serum tumor marker content, immune cell level and activity in peripheral blood and KPS score before treatment (P> 0.05). After treatment, serum tumor markers were lower than those in control group, and immune cell level, NK cell-related activity and KPS score were higher than those in control group (P< 0.05). SBRT plus immunotherapy can reduce the level of various tumor markers, improve the immune status and quality of survival for NSCLC patients.

Translational History and Hope of Immunotherapy of Canine Tumors.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, make them ideal subjects for studying cancer therapies. Tumors like osteosarcoma, hemangiosarcoma, soft-tissue sarcoma, and non-Hodgkin lymphoma occur with greater frequency than their counterpart disease in humans. Canine brain tumors allow the study of therapy strategies with imaging, surgery, and radiotherapy equipment in veterinary patients with near-human geometry. Nonspecific immunostimulants, autologous and allogeneic vaccines, immune checkpoint inhibitors, and cellular therapies used in treating canine cancers have been tested in veterinary clinical trials. These treatments have not only improved outcomes for dogs but have also provided valuable insights for human cancer treatment. Advancements in radiation technology and the development of tools to characterize canine immune responses have further facilitated the ability to translate veterinary clinical trial results to human applications. Advancements in immunotherapy of canine tumors have directly supported translation to human clinical trials leading to approved therapies for patients with cancer around the world. The study of immunotherapy in dogs has been and will continue to be a promising avenue for advancing human cancer treatment.

GPS-Net: discovering prognostic pathway modules based on network regularized kernel learning.

The search for prognostic biomarkers capable of predicting patient outcomes, by analyzing gene expression in tissue samples and other molecular profiles, remains largely on single-gene-based or global-gene-search approaches. Gene-centric approaches, while foundational, fail to capture the higher-order dependencies that reflect the activities of co-regulated processes, pathway alterations, and regulatory networks, all of which are crucial in determining the patient outcomes in complex diseases like cancer. Here, we introduce GPS-Net, a computational framework that fills the gap in efficiently identifying prognostic modules by incorporating the holistic pathway structures and the network of gene interactions. By innovatively incorporating advanced multiple kernel learning techniques and network-based regularization, the proposed method not only enhances the accuracy of biomarker and pathway identification but also significantly reduces computational complexity, as demonstrated by extensive simulation studies. Applying GPS-Net, we identified key pathways that are predictive of patient outcomes in a cancer immunotherapy study. Overall, our approach provides a novel framework that renders genome-wide pathway-level prognostic analysis both feasible and scalable, synergizing both mechanism-driven and data-driven for precision genomics.

Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.

Biliary tract cancer (BTC) represents a challenging malignancy characterized by aggressive behavior, high relapse rates, and poor prognosis. In recent years, immunotherapy has revolutionized the treatment landscape for various cancers, but its efficacy in BTC remains limited. This article provides a comprehensive overview of the advances in preclinical and clinical studies of immunotherapy for BTC. We explore the potential of immune checkpoint inhibitors in reshaping the management of BTC. Despite disappointing results thus far, ongoing clinical trials are investigating the combination of immunotherapy with other treatment modalities. Furthermore, research on the tumor microenvironment has unveiled novel targets for immunotherapeutic interventions. By understanding the current state of immunotherapy in BTC and highlighting future directions, this article aims to fuel further exploration and ultimately improve patient outcomes in this challenging disease.