Understanding Of Immunotherapy Research Articles

Characterization of neutrophil extracellular traps related gene pair for predicting prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant disease with a high incidence rate, high mortality and poor prognosis. Neutrophil extracellular traps (NETs), as an extracellular reticular structure, promote the development and progression of cancer in the tumor microenvironment, and have a promising prospect as a prognostic indicator. In the present study, we elucidated the prognostic value of NET-related genes. The NETs gene pair of The Cancer Genome Atlas cohort was constructed by least absolute shrinkage and selection operator analysis. Samples from the International Cancer Genome Consortium were performed to verify its feasibility. Kaplan-Meier analysis was used to compare the overall survival (OS) rate of the two subgroups. The independent predictors of OS were determined by univariate and multivariate Cox analysis. Furthermore, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed by gene set enrichment analysis. The single sample gene set enrichment analysis method was performed to deplore the relationship of risk score with tumor immune microenvironment. The GSE149614 dataset was applied as single cell RNA level validation. PCR was performed to the detect mRNA expression profiles of NETs-related genes. Our analysis of the NETs-related model provides a promising prospect as a prognostic indicator. The OS of high-risk group patients was significantly reduced. The risk score was an important independent predictor of HCC prognosis. The Nomogram model suggested a favorable classification performance. The drug resistance and sensitivity of tumor cells to chemotherapeutics was significantly correlated with the prognostic gene expression. The immune status of the two risk groups showed a marked difference. The novel prognostic gene pair and immune landscape could predict the prognosis of HCC patients and provide a new understanding of immunotherapy in HCC.

Characterization of the tumor microenvironment by highly multiplexed microscopy

Malignant neoplasms are highly complex ecosystems consisting of tumor cells and the tumor microenvironment (TME), which is composed of structural elements (vessels, fibroblasts, extracellular matrix) and awide variety of infiltrating immune cell types of the innate and adaptive immune systems. The TME is the main site of tumor cell-immune cell interactions and plays acritical role in antitumoral immunity. Immunotherapies can affect the interactions between immune cell types and tumor cells in the TME, boost immune responses, and lead to tumor elimination. Novel highly multiplexed microscopy techniques, which enable the detection of more than50 simultaneous markers in tissues, facilitate the in-depth characterization of the TME at single-cell resolution in clinically relevant samples. Detailed knowledge about the cellular and spatial composition of the TME, the specific cell types and their functional properties, and cell-cell interactions-as revealed by highly multiplexed microscopy-will improve our understanding of immunotherapies' mechanisms of action and reveal new potential therapeutic targets and predictive biomarkers.

Using CD69 PET Imaging to Monitor Immunotherapy-Induced Immune Activation.

Immune checkpoint inhibitors (ICI) have been effective in treating a subset of refractory solid tumors, but only a small percentage of treated patients benefit from these therapies. Thus, there is a clinical need for reliable tools that allow for the early assessment of response to ICIs, as well as a preclinical need for imaging tools that aid in the future development and understanding of immunotherapies. Here we demonstrate that CD69, a canonical early-activation marker expressed on a variety of activated immune cells, including cytotoxic T cells and natural killer (NK) cells, is a promising biomarker for the early assessment of response to immunotherapies. We have developed a PET probe by radiolabeling a highly specific CD69 mAb, H1.2F3, with Zirconium-89 (89Zr), [89Zr]-deferoxamine (DFO)-H1.2F3. [89Zr]-DFO-H1.2F3 detected changes in CD69 expression on primary mouse T cells in vitro and detected activated immune cells in a syngeneic tumor immunotherapy model. In vitro uptake studies with [89Zr]-DFO-H1.2F3 showed a 15-fold increase in CD69 expression for activated primary mouse T cells, relative to untreated resting T cells. In vivo PET imaging showed that tumors of ICI-responsive mice had greater uptake than the tumors of nonresponsive and untreated mice. Ex vivo biodistribution, autoradiography, and IHC analyses supported the PET imaging findings. These data suggest that the CD69 PET imaging approach detects CD69 expression with sufficient sensitivity to quantify immune cell activation in a syngeneic mouse immunotherapy model and could allow for the prediction of therapeutic immune responses to novel immunotherapies.

Virus-Based Immuno-Oncology Models.

Immunotherapy has been extensively explored in recent years with encouraging results in selected types of cancer. Such success aroused interest in the expansion of such indications, requiring a deep understanding of the complex role of the immune system in carcinogenesis. The definition of hot vs. cold tumors and the role of the tumor microenvironment enlightened the once obscure understanding of low response rates of solid tumors to immune check point inhibitors. Although the major scope found in the literature focuses on the T cell modulation, the innate immune system is also a promising oncolytic tool. The unveiling of the tumor immunosuppressive pathways, lead to the development of combined targeted therapies in an attempt to increase immune infiltration capability. Oncolytic viruses have been explored in different scenarios, in combination with various chemotherapeutic drugs and, more recently, with immune check point inhibitors. Moreover, oncolytic viruses may be engineered to express tumor specific pro-inflammatory cytokines, antibodies, and antigens to enhance immunologic response or block immunosuppressive mechanisms. Development of preclinical models capable to replicate the human immunologic response is one of the major challenges faced by these studies. A thorough understanding of immunotherapy and oncolytic viruses’ mechanics is paramount to develop reliable preclinical models with higher chances of successful clinical therapy application. Thus, in this article, we review current concepts in cancer immunotherapy including the inherent and synthetic mechanisms of immunologic enhancement utilizing oncolytic viruses, immune targeting, and available preclinical animal models, their advantages, and limitations.

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment.

Simple SummaryImmunotherapies have changed the way we treat cancer and, while some patients have benefitted greatly, there are still those that do not respond to therapy. Understanding why some patients respond to therapy and others do not is critical in developing new immunotherapeutic strategies. The increasing awareness of the importance of investigating the tumour in its entirety, including the surrounding tissue and role of various immune cells is helping to differentiate responders and non-responders. In addition, the resolution gained by the development of sophisticated bioinformatic technologies allows for a deeper understanding of the complex roles of individual cells in the tumour. This advancement will be critical for the development of novel therapies to treat cancer.Immunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far. A significant focus to date has been the identification of specific markers associated with response to immunotherapy. Unfortunately, the heterogeneity between patients and cancer types means identifying markers of response to therapy is inherently complex. There is a growing appreciation for the role of the tumour microenvironment (TME) in directing response to immunotherapy. The TME is highly heterogeneous and contains immune, stromal, vascular and tumour cells that all communicate and interact with one another to form solid tumours. This review analyses major cell populations present within the TME with a focus on their diverse and often contradictory roles in cancer and how this informs our understanding of immunotherapy. Furthermore, we discuss the role of integrated omics in providing a comprehensive view of the TME and demonstrate the potential of leveraging multi-omics to decipher the underlying mechanisms of anti-tumour immunity for the development of novel immunotherapeutic strategies.

Identification of molecular subtyping system and four-gene prognostic signature with immune-related genes for uveal melanoma.

Immunotherapy is the most promising treatment for uveal melanoma patients with metastasis. Tumor microenvironment plays an essential role in tumor progression and greatly affects the efficacy of immunotherapy. This research constructed an immune-related subtyping system and discovered immune prognostic genes to further understand the immune mechanism in uveal melanoma. Immune-related genes were determined from literature. Gene expression profiles of uveal melanoma were clustered using consensus clustering based on immune-related genes. Subtypes were further divided by applying immune landscape, and weighted correlation network analysis was performed to construct immune gene modules. Univariate Cox regression analysis was conducted to generate a prognostic model. Enriched immune cells were determined after gene set enrichment analysis. Three major immune subtypes (IS1, IS2, and IS3) were identified, and IS2 could be further divided into IS2A and IS2B. The subtypes were closely associated with uveal melanoma prognosis. IS3 group had the most favorable prognosis and was sensitive to PD-1 inhibitor. Immune genes in IS1 group showed an overall higher expression than IS3 group. Six immune gene modules were identified, and the enrichment score of immune genes varied within immune subtypes. Four immune prognostic genes (IL32, IRF1, SNX20, and VAV1) were found to be closely related to survival. This novel immune subtyping system and immune landscape provide a new understanding of immunotherapy in uveal melanoma. The four prognostic genes can predict prognosis of uveal melanoma patients and contribute to new development of targeted drugs.

FP02.04 Immunotherapy in Lung Cancer: Analysis of Patients’ Awareness and Perceptions

Scientific advances in immuno-oncology have contributed to improved survival of lung cancer patients, and immunotherapy is part of the daily clinical practice. Due in part to these hopeful results, immunotherapy is a relatively popular subject in mass media. The scientific community has undertaken significant efforts to educate and inform patients about several aspects of immunotherapy, particularly regarding some common misconceptions, but the results are inconclusive and anecdotal. CareAcross, a digital multilingual platform which provides personalized, evidence-based support to cancer patients undertook the initiative to investigate the level of education and information of cancer patients regarding immunotherapy. From June 2020 to February 2021, specific questions were posed to the members of the CareAcross online platform. Members were predominantly from the UK, France, Spain, Italy or Germany, and were diagnosed with lung, breast, colorectal or prostate cancer. Their responses were correlated with other characteristics of their health profile and cancer journey. This analysis focuses on lung cancer patients, and compares the perceptions of those who have received immunotherapy vs those who have not. Among 5589 responders, 1131 had lung cancer; 241 had received immunotherapy (21%; henceforth “IO-treated”) while the rest had not (890 or 79%; henceforth “non-IO-treated”). Regarding the mechanism of action, 29% of patients responded either “do not know” or ”not sure”; non-IO-treated were the least aware subgroup (33% vs 11% of IO-treated). Regarding the timing of action, 28% of patients reported knowing that immunotherapy starts working some time after treatment initiation (41% of IO-treated vs 24% of non-IO-treated). 44% of patients could not respond (22% of IO-treated vs 50% of non-IO-treated). Most patients (77%) were confident that chemotherapy causes more side-effects than immunotherapy (86% of IO-treated vs 74% of non-IO-treated) and only 3% of all believed the opposite. The main difference was observed regarding ignorance: 8% of IO-treated were unaware, compared to 23% of non-IO-treated. When comparing immunotherapy’s toxicity with that of targeted therapies, more than half of all subgroups did not know. While all subgroups believed that immunotherapy was the least toxic of the two, IO-treated were the most ambivalent, resulted in a smaller gap (with 20% considering immunotherapy more toxic than targeted therapy, vs 24% for the opposite). Regarding the perception of costs to the healthcare system, 21% believe that immunotherapy costs more than targeted and chemotherapy (35% of IO-treated vs 17% of non-IO-treated). Each of the other two modalities were considered the most expensive by 12% of each subgroup, across the board. The remainder was accounted for by those who did not know (50% of all; 40% of IO-treated vs 53% of non-IO-treated) or believe they cost the same (5%; 3% of IO-treated vs 5% of non-IO-treated). The overall understanding of immunotherapy, its mechanism of action, impact, and costs, is still relatively low, even among lung cancer patients who have received such treatment. Given immunotherapy’s growing applicability, these findings highlight the need for broader, continuous and frequently updated patient education initiatives. These can improve knowledge, instill confidence, reduce misconceptions, and enhance patient-clinician collaboration.

Single-cell Analysis Technologies for Immuno-oncology Research: from Mechanistic Delineation to Biomarker Discovery

The successes with immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR)-T-cell therapy in treating multiple cancer types have established immunotherapy as a powerful curative option for patients with advanced cancers. Unfortunately, many patients do not derive benefit or long-term responses, highlighting a pressing need to perform complete investigation of the underlying mechanisms and the immunotherapy-induced tumor regression or rejection. In recent years, a large number of single-cell technologies have leveraged advances in characterizing immune system, profiling tumor microenvironment, and identifying cellular heterogeneity, which establish the foundations for lifting the veil on the comprehensive crosstalk between cancer and immune system during immunotherapies. In this review, we introduce the applications of the most widely used single-cell technologies in furthering our understanding of immunotherapies in terms of underlying mechanisms and their association with therapeutic outcomes. We also discuss how single-cell analyses help to deliver new insights into biomarker discovery to predict patient response rate, monitor acquired resistance, and support prophylactic strategy development for toxicity management. Finally, we provide an overview of applying cutting-edge single-cell spatial-omics to point out the heterogeneity of tumor–immune interactions at higher level that can ultimately guide to the rational design of next-generation immunotherapies.

Abstract PS9-15: Utilizing education to strengthen oncologist' understanding of immunotherapy in triple negative breast cancer

Abstract Background:Immunotherapy was first introduced into the treatment of triple negative breast cancer with the approval of nab-paclitaxel + atezolizumab in patients with metastatic PD-L1-positive disease. Continued research sheds light on the utility of other immuontherapies in the metastatic setting as well as a potential role for immunotherapy in neoadjuvant disease. Given the factors impacting patient eligibility and the rationale for further exploring immunotherapy in novel settings, education can help ensure that oncologists are well-informed about available clinical trial data and ongoing research to optimize the use of immunotherapy in this subtype of breast cancer. The goal of this study was to determine if participation in an educational activity can improve the knowledge and competency of oncologists on the application of checkpoint inhibitors in the treatment of triple negative breast cancer.Methods: An online continuing education (CME) activity consisted of a 30-minute video discussion with synchronized slides between 2 panelists about the rationale and ongoing clinical trials exploring data for immunotherapy in triple negative breast cancer. Educational effect was assessed using a repeated pairs pre-assessment/post-assessment study design and compared of content-based pre- and post-assessment responses. A chi-square test was used to identify statistical differences between pre- and post-assessment responses. P values were calculated and those < 0.05 were considered statistically significant. Data from oncologist participants in the educational activity were collected between 3/22/20 through 5/19/20. Results:Participation in education resulted in statistically significant improvement and a considerable educational effect for oncologists (n=121; p <0.0001). 61% of oncologists reported practicing in a community setting with 67% treating patients beyond breast cancer alone. Overall, oncologists demonstrated a 20% increase in confidence in identifying the role and stage in triple negative breast cancer therapy for the use of immune checkpoint inhibitors. Improvements in knowledge were observed in: •Understanding the biological rationale for using immune checkpoint inhibitors in patients with triple negative breast cancer (69% vs. 83%; p <0.05) •Knowing the ongoing clinical trials that may impact the use of immune checkpoint inhibitors across the continuum of TNBC (69% vs. 87%; p <0.01) •Emerging clinical trial data on the use of immune checkpoint inhibitors utilizing pathologic complete response as an endpoint of efficacy in neoadjuvant disease (73% vs. 82%) Conclusions: This online, interactive, CME-certified educational activity resulted in significant overall gains in oncologist knowledge regarding the existing and emerging evidence for immunotherapy in triple negative breast cancer. These results demonstrate the effectiveness of on-demand education but also highlight the effectiveness in reaching community-based practitioners and also practitioners that do not specialize in breast cancer alone. Grantors: This educational initiative was supported through educational grants from Bristol Myers Squibb and Merck & Co., Inc. Citation Format: Kinjal Parikh, Charlotte Warren, Patrick Kugel, Ann Carothers, Haleh Kadkhoda, Leisha Emens. Utilizing education to strengthen oncologist' understanding of immunotherapy in triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-15.

How to select cancer patients for immunotherapy.

In recent years, the importance and understanding of immunotherapy in the treatment of solid tumours has increased dramatically. Presently, immune checkpoint inhibitors (ICIs) are the most widely used immunotherapy and are approved for several indications across different solid malignancies, such as malignant melanoma, non-small cell lung carcinoma, renal cell carcinoma, and bladder cancer [1]. In addition, ICI have shown considerable activity in microsatellite instable tumours (MSI), irrespective of the tissue of origin [2,3].

Leveraging Immunotherapy with Nanomedicine

AbstractConsiderable progress has been made in the development and understanding of immunotherapy, notably with the emergence of novel chimeric antigen receptor T cells (CAR‐T) which changed the perception of personalized therapy. However, cell‐based immunotherapy not only lacks therapeutic efficiency in various solid cancers but also raises concerns related to important side effects. The convergence of immunotherapy and nanomedicine is timely as nanoparticles can now be easily conjugated to various antibodies and peptides enabling outstanding abilities to target specific cell populations in vivo. Here, the state of the art of immunonanotherapy that activates the immune system in vivo, by acting either as vaccines or as tumor microenvironment (TME) activators is described. Then, the development of ex vivo immune‐cell surface labeling strategies is discussed to exploit immune cells as trojan horses and thereby improving the delivery of the therapeutics in the TME. Such a strategy is likely to considerably amplify the efficacy of immunotherapy.

Not just 'immunity': how the microbiota can reshape our approach to cancer immunotherapy.

Cancer immunotherapy refers to a set of approaches aiming at enhancing the immune system to fight cancer growth and spread. This variety of therapeutic approaches, especially those inhibiting immune checkpoints, have shown very promising results. Nevertheless, patients may respond differently to treatments and the efficacy of immunotherapy seems to be dependent on several factors that go beyond the molecular targeting of immune cells modulation. Here, we review how the activity of gut microbiota appears to be crucial in determining the effectiveness of some immunotherapeutic treatments, fostering or impeding the conditions under which treatments can work or not. Moreover, we discuss how these findings suggest not only extending the range of immunotherapeutic approaches but also reshaping our understanding of immunotherapy itself.

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Evaluation of awareness and understanding of cancer immunotherapy among healthcare professionals in eastern Saudi Arabia.

Cancer immunotherapy is a complicated field that develops rapidly; in the past decades, immunotherapy has become the standard treatment for several cancer types. The aim of the current study was to estimate the awareness and understanding of cancer immunotherapy and associated immunological concepts among healthcare professionals (HCPs) in eastern Saudi Arabia in order to assess educational needs. A cross-sectional questionnaire was conducted among multidisciplinary HCPs in healthcare institutions in eastern Saudi Arabia from April 2019 to June 2019. The survey was designed to assess the awareness and understanding of HCPs' basic scientific knowledge of cancer immunotherapy. The data were analyzed using the Statistical Package for the Social Sciences (SPSS). Reliability was tested through Cronbach's alpha, and a χ2 or Fisher's exact test was used to determine the distribution of categorical variables between groups. The study included 360 HCPs: 43.6% physicians, 21.9% nurses, 20.8% medical laboratory scientists, and 13.6% pharmacists. Only 20.6% of the HCPs considered immunotherapy the best-known cancer therapy. The overall level of awareness of cancer immunotherapy was low (55.8%), and only 6.4% of the participants had a high knowledge rate. The majority of the respondents indicated the importance of studying the science of immunotherapy. Cronbach's alphas for the HCPs' perceptions, self-evaluation rate, and reflection scales were 0.74, 0.90, and 0.66, respectively. Simple linear regression showed a significant relationship between reflection and self-evaluation. A reliable and consistent study revealed a low level of awareness and understanding of immunotherapy among multidisciplinary HCPs.

Immunocyte Profiling Using Single-Cell Mass Cytometry Reveals EpCAM+ CD4+ T Cells Abnormal in Colon Cancer.

Colon cancer (CC) is one of the leading causes of cancer related mortality. Research over past decades have profoundly enhanced our understanding of immunotherapy, a major clinical accomplishment, and its potential role toward treating CC. However, studies investigating the expression of these immune checkpoints, such as epithelial cell adhesion molecule (EpCAM), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1), by peripheral blood mononuclear cells (PBMCs) is lacking. Here, high-dimensional mass cytometry (CyTOF) is used to investigate immune alterations and promising immunotherapeutic targets expression by PBMCs of CC patients. Results reveal that expression of EpCAM and PD-L1 on CD4+ T cells significantly increased in patients with CC, compared with age- and sex- matching healthy controls and patients with colonic polyps. These differences are also validated in an independent patient cohort using flow cytometry. Further analysis revealed that EpCAM+ CD4+ T cells are PD-L1+ CCR5+ CCR6+. Immunofluorescence staining results demonstrate that the increase of EpCAM+ CD4+ T cells is also observed in tumor tissues, rather than para-cancerous tissues. To ascertain the functional disorders of the identified cell subset, phosphorylated signaling protein levels are assessed using imaging mass cytometry. Increases in pp38 MAPK and pMAPKAPK2 are observable, indicating abnormal activation of pp38 MAPK-pMAPKAPK2 signaling pathway. Results in this study indicate that EpCAM+ CD4+ T cells may play a role in CC development. Detailed knowledge on the functionality of EpCAM+ CD4+ T cells is of high translational relevance.

Balancing the Hype with Reality: What Do Patients with Advanced Melanoma Consider When Making the Decision to Have Immunotherapy?

Immunotherapy has resulted in unprecedented improvements in survival and maintained quality of life for many patients with advanced melanoma. However, durable responses are observed in only a minority of patients, and severe treatment side effects are experienced by 5%-30%. There are no reliable tests that can differentiate between patients who are likely to respond to immunotherapy and those who will not. Hence, new challenges have arisen as clinicians try to facilitate patients in their decision-making regarding immunotherapy. Furthermore, little is known about the real-world patients' experience and understanding of immunotherapy outside the clinical trial setting. Here, we explore the perspectives of patients undergoing immunotherapy for melanoma and focus on factors that influenced their treatment decision-making. Twenty-three in-depth semistructured interviews were conducted with patients receiving pembrolizumab for stage IV melanoma at an Australian public cancer hospital. Patients were recruited at a range of time points after commencing therapy, and their experience of treatment was explored. Interviews were audio recorded, transcribed verbatim, coded, and analyzed thematically. Immunotherapy is viewed as a symbol of hope, with high-profile anecdotes reinforcing this perception. Only a minority of patients expressed a good understanding of the likely efficacy and potential treatment side effects. Patients are reliant on their clinicians' recommendation regarding immunotherapy treatment decisions. Novel treatments such as immunotherapy provide significant hope for patients. This may influence their preference for immunotherapy over and above the usual considerations of the trade-off between efficacy and toxicity. Careful counsel and individualized patient resources may further facilitate treatment decision-making. This study highlighted some of the misconceptions held by patients that need to be addressed when discussing the possibility of receiving treatment with immunotherapy for advanced melanoma. Patients placed a lot of importance on high-profile anecdotes rather than truly understanding likely outcomes of treatment based on personal circumstances. The majority of patients had a poor understanding of the potential side effects and long-term implications of treatment with immunotherapy. Careful counsel is required in order to facilitate informed decision-making about treatment and to ensure possible side effects are known and appreciated. Further research is needed to develop tools to aid decision-making in everyday clinical practice.

Reasoning the effect of immunotherapy after chemoradiation in the PACIFIC trial.

Durvalumab consolidation after chemoradiation has been a giant leap in the treatment of stage III non-small-cell lung cancer with an unprecedented 16.8-month median progression-free survival. PACIFIC trial is a new foray into chemoimmunotherapy trials where we apply our knowledge of 'immunogenic cell death' and 'Abscopal' effect of radiation in the clinic.Our understanding of immunotherapy after chemoradiation treatment and application of immunogenic cell death biomarkers in future trials may be the approach we need to maximize benefit of these treatments in the appropriate patients.

Abstract 3630: Deep and durable response with dual anti-CTLA-4 and PD-1 blockade in mismatch repair (MMR) proficient endometrial cancer

Abstract Immune checkpoint inhibitors have shown promising efficacy in multiple cancer types, but have yet to be extensively validated in endometrial cancer. However, the recent FDA approval of PD-1 inhibitors for mismatch repair (MMR) deficient tumors has extended use of these treatments to all cancer types. PD-L1 positivity in tumor tissue has also been shown to predict susceptibility to immunotherapy and has been used to guide use of these treatments. Despite these advances, the response to immunotherapy in endometrial cancer remains poorly understood. Here, we describe the case of a patient with MMR proficient, PD-L1-negative stage IV endometrial cancer with positive response to combination PD-1 and CTLA-4 inhibition. The patient initially presented with ascites and elevated tumor markers, and cytology from peritoneal fluid showed endometrial adenocarcinoma with squamous and mucinous differentiation and clear cell features. She underwent surgical debulking with both neoadjuvant and adjuvant cycles of docetaxel and carboplatin, but unfortunately had progressive metastatic disease within 4 months. The patient declined further chemotherapeutic agents, and thus was instead trialed on combination nivolumab and ipilimumab despite her cancer exhibiting MMR proficiency and negative PD-L1. She demonstrated deep and durable on-going partial response to this treatment that has persisted still after 10 months. Her course has notably been complicated by hypophysitis that manifested after 5 months of treatment as worsening fatigue, but she has been able to continue with her treatment regimen. This case indicates the potential existence of an endometrial cancer subtype that is sensitive to immune checkpoint blockade, but based on mechanisms other than those driven by MMR deficiency or PD-L1 positivity. Improved understanding of immunotherapy in advanced endometrial cancer is clearly needed and offers the potential to significantly enhance patient outcomes. Citation Format: Michael S. Oh, Young Chae. Deep and durable response with dual anti-CTLA-4 and PD-1 blockade in mismatch repair (MMR) proficient endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3630.

Immunotherapy awareness in the oncology patient population: An Irish hospital experience.

e15160Background: To identify cancer patients’ awareness, experience and understanding of immunotherapy, as well as factors influencing their acceptance of treatment. Methods: This study was undert...