tbuckley/cabot-search huggingface dataset:
Abstract 10658: Patients Receive Better Care in a Traditional Randomized Trial Setting Than in a Pragmatic Quality Improvement Study: Potential Implications for Improvements in Care
Authors: Brittany Chapman, John J McMurray, Adam D Devore, Larry A Allen, Bradi B Granger, Neha J Pagidipati, Lisa Kaltenbach, Renato D Lopes, Christopher B Granger
Journal: Circulation (2021)

Introduction: Use of guideline-directed medical therapy (GDMT) is suboptimal in practice and often better in patients enrolled in clinical trials. We sought to investigate whether care differed for patients with heart failure with reduced ejection fraction (HFrEF) recently enrolled in a pharmaceutical trial versus those in a pragmatic implementation study. Methods: DAPA-HF was a randomized trial of dapagliflozin versus placebo that included patients with HFrEF, and standard background GDMT was required unless contraindicated or not tolerated. CONNECT-HF was a site-level cluster randomized pragmatic trial that included patients discharged after admission for decompensated HFrEF, with the goal of improving GDMT at one year. Each study required patient informed consent. Medication use data includes the total population at the time of enrollment in DAPA-HF and at one year in CONNECT-HF. Results: CONNECT-HF enrolled U.S. patients who were younger, more likely female, and more often Black (Table 1). Patients in DAPA-HF had significantly higher use of all classes of GDMT at any dose and at ≥ 50% target dose (Figure 1). Unadjusted mortality was lower in DAPA-HF (Table 1). Conclusions: Use of GDMT was substantially better and mortality was lower in a traditional randomized trial than in a pragmatic implementation trial. Whether this is due to differences in the populations, site care teams, or intensity of care and monitoring is unknown. The protocol-driven aspects of traditional trials are worthy of further study to improve care provided in standard practice. These observations also support inclusion of patients in randomized trials given the excellent care and outcomes in that setting.
Treatment-Free Intervals during CD19xCD3 BiTE ® Construct-Mediated T-Cell Stimulation Induce Functional Reinvigoration and Transcriptional Reprogramming of Exhausted T Cells
Authors: Nora Zieger, Maryam Kazerani Pasikhani, Tobias Straub, Alyssa Nicholls, Gerulf Hänel, Jan Wulf, Michaela Scheurer, Daniel Nixdorf, Monika Sponheimer, Sonja M Lacher, Bettina Brauchle, Anetta Marcinek, Lisa Rohrbacher, Alexandra Leutbecher, Michael von Bergwelt, Karsten Spiekermann, Oliver Weigert, Sebastian Theurich, Veit L Buecklein, Roman Kischel, Marion Subklewe
Journal: Blood (2021)
Abstract 12793: Characterization of Isogenic Human IPSC Engineered Cardiac Tissue Deficient in Cardiac Myosin Binding Protein C Indicates a Primary Calcium-Handling Abnormality
Authors: Willem J De Lange, Emily T Farrell, John C Ralphe
Journal: Circulation (2021)

Mutations that cause truncation of cardiac myosin binding protein C (cMyBP-C) are common causes of hypertrophic cardiomyopathy (HCM), and cause disease through a mechanism of haploinsufficiency. Recent studies in isogenic iPSC-cardiomyocyte (CM) heterozygous for cMyBP-C truncation, show normal cMyBP-C protein levels, suggesting a different mechanism. Though rare, cases of patients homozygous for cMyBP-C truncations, present with early postnatal cardiomyopathy rapidly progressing to heart failure. We postulated that human iPSC-ECTs would present with a hypercontractile phenotype with accelerated contractile kinetics, similar to cMyBP-C -/- mouse ECTs. We introduced homozygous (-/-) and heterozygous (+/-) frameshifts in cMyBP-C in iPSCs by CRISPR gene editing followed by differentiation into CM which were incorporated into ECTs. Although cMyBP-C protein levels were similar in +/- and +/+ 2D CM, the level of cMyBP-C was reduced in +/- ECTs (0.25 vs. 0.49; p = 0.007; N ≥ 8,) and was absent in -/- ECTs. Functional characterization revealed slow Ca 2+ -handling that became more pronounced with prolonged time in culture (Ca 2+ T 100 : 110.9 vs. 76.0 ms; p = 0.0006; N ≥ 7) and normal Ca 2+ -sensitivity, without pronounced differences in contractile function in +/- ECTs. In addition to slow Ca 2+ -handling, -/- ECTs (Ca 2+ T 100 : 133.3 vs. 76.0 ms; p &lt; 0.0001; N ≥ 8) also present with decreased Ca 2+ -transient (0.24 vs. 0.65 F 340 /F 380 ; P = 0.002; N ≥ 8) and twitch (3.93 vs. 10.30 mN/mm 2 ; p &lt; 0.0001; N ≥ 21) amplitudes, and slow late relaxation (RT 50-90 120.0 vs. 95.1 ms; p &lt; 0.0001; N ≥ 21) that became more pronounced with prolonged time in culture. When permeabilized, -/- ECT displayed a right-shift in Ca 2+ -sensitivity (pCa 50 5.87 vs. 5.98; p &lt; 0.0001; N ≥ 11) and a decrease in Hill-coefficient (2.24 vs. 2.98; p = 0.0006; N ≥ 11). In our living 3D in vitro tissue culture system, heterozygous truncation of cMyBP-C causes haploinsufficiency and demonstrates a slow Ca 2+ -release with minimal contractile abnormalities, while -/- ECTs present with a hypocontractile phenotype, likely mediated by aberrant Ca 2+ handling and sensitivity. These findings reinforce that Ca 2+ -mishandling is a primary defect in cMyBP-C HCM, and therefore represents a target for therapeutical intervention.
Prognostic Scoring Systems in Diffuse Large B Cell Lymphoma Patients - Is Kyoto Prognostic Index an Added Value?
Authors: Marilia Gomes, Sara Duarte, Carolina Afonso, Dulcelena Neves, Bárbara Almeida Marques, Carla Barros Lima, Adriana Roque, Ana Catarina Lai, Lenka Ruzickova, Maria José Julião, José Pedro Carda, Ana Espadana
Journal: Blood (2021)
CTNI-18. PHASE I AND PRELIMINARY PHASE 0 RESULTS OF ABTC 1801: A MULTI-ARM CLINICAL TRIAL OF THE PARP INHIBITOR PAMIPARIB (BGB290) WITH VERY LOW DOSE METRONOMIC TEMOZOLOMIDE IN RECURRENT IDH MUTANT GLIOMAS
Authors: David Schiff, Ranjit Bindra, Jing Li, Xiaobu Ye, Benjamin Ellingson, Tobias Walbert, Jian Campian, L Burt Nabors, Frank Lieberman, Byran Ozer, Arati Desai, Antonio Omuro, Patrick Wen, Serena Desideri, Joy Fisher, Stuart Grossman
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Preclinical studies have demonstrated that IDH1-mutant (IDHmt) gliomas harbor a BRCAness phenotype with a defect in homologous recombination that confers PARP inhibitor sensitivity. Pamiparib (BeiGene BGB-290) is an effective PARP-trapping PARP inhibitor with demonstrated favorable brain penetration in animal models. METHODS ABTC 1801 is a study examining the safety, pharmacokinetics, and efficacy of the combination of pamiparib with low dose metronomic temozolomide in recurrent IDHmt gliomas. The Phase I component utilized a 3 + 3 design with a target DLT rate ≤ 33%. Pamiparib dose was 60 mg BID and temozolomide dose 20 mg daily, with dose de-escalation levels for anticipated hematological toxicity. RESULTS Seven patients were enrolled on the Phase I portion at dose level 1; one patient was replaced for inadequate dosing secondary to non-compliance. All patients had prior radiotherapy and temozolomide; 4/7 had received multiple lines of alkylator therapy including nitrosoureas. Median age was 45, KPS 90, and number of prior relapses 3. Four patients had anaplastic astrocytoma, 2 anaplastic oligodendroglioma, and 1 glioblastoma. One of 6 patients (16.7%) experienced DLT during the first cycle (grade 3 neutropenia and thrombocytopenia). Two additional patients had grade 2 neutropenia. Two patients remain on study treatment at 12+ and 10+ months, while a third progressed at 10.1 months (PFS-6 43%). Tumor tissue was collected from two patients in the surgical arm. In enhancing and non-enhancing tumors, the mean unbound pamiparib concentrations were 198 and 160 nmol/L (or nmol/kg), respectively, which were &amp;gt; 20-fold the in vitro IC50 for PARP inhibition; mean unbound tumor-to-plasma ratios were 0.65 and 0.38. CONCLUSIONS Phase I results support pamiparib 60 mg BID with temozolomide 20 mg daily as the dosages for the Phase II study. Preliminary Phase 0 data suggest that pamiparib likely achieves sufficient pharmacologically active concentrations in both enhancing and non-enhancing brain tumors.
Abstract 13802: J Waves Observed in More Than 3 Electrocardiographic Leads Predict the Presence of Organized Myocardial Fibrotic or Fat Change in Non Ischemic Survivors of Ventricular Fibrillation
Authors: Nobusada Funabashi, Kohki Nakamura, takehio sasaki, Shigeto Naito, Yoshio Kobayashi
Journal: Circulation (2021)

Introduction: The distribution of J waves and the presence of organized left ventricular (LV) myocardial damage may be related in non ischemic survivors of ventricular fibrillation (VF). Hypothesis: We hypothesize that the distribution of J waves can predict the presence of myocardial damage such as fibrotic or fat change in non ischemic survivors of VF. Methods: We conducted a retrospective analysis of 16 survivors of VF (12 males; 60±15 years) without any histories of previous myocardial infarction and underwent cardiac CT in which no significant coronary stenosis were observed and/or MRI before implantation of a cardioverter defibrillator. Results: On ECG, 3 patients had atrial fibrillation and 12 had J waves. On CT and/or MRI, 7 patients had organized LV myocardial fibrotic and/or fat change. The mean corrected QT interval was 451±47 and 415±5 msec in patients with and without J waves (P=0.147) and 458±32 and 429±48 msec in patients with and without myocardial fibrotic and/or fat change (P=0.202), respectively. The distribution of J waves was presented in the table. Presence of the J waves observed more than 3 ECG leads (N=4) and presence of myocardial fibrotic and/or fat change (N=7) significantly correlated each other in the Fisher's exact test (P=0.019). Presence of myocardial fibrotic and/or fat change were significantly greater in patients with J waves observed more than 3 ECG leads than those with J waves observed less than 4 ECG leads (100% vs 25%, P=0009). Presence of J waves observed more than 3 ECG leads were also significantly greater in patients with myocardial fibrotic and/or fat change than those without (57% vs 0%, P=0009). Conclusions: In non ischemic survivors of VF, if J waves were observed more than 3 ECG leads, the frequency of LV myocardial fibrotic and/or fat change was significantly higher than those without. The distribution and numbers of ECG leads with J waves and the presence of myocardial fibrotic and/or fat change may be useful to predict non ischemic VF.
A Study of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, for Patients with Frontline and Relapsed/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Authors: Naveen Pemmaraju, Giovanni Marconi, Elisabetta Todisco, Pau Montesinos, Andrew A. Lane, Kendra Sweet, Eunice S. Wang, Eric Deconinck, David A Rizzieri, Roland B. Walter, Ahmed Aribi, Delphine Lebon, Moshe Y. Levy, Luca Mazzarella, Giovanni Martinelli, Federica Gigli, Harry P. Erba, Evelyn Acuña-Cruz, Marina Konopleva, Hagop Kantarjian, Callum M Sloss, Jiuzhou Wang, Kara E Malcolm, Patrick A Zweidler-McKay, Daniel J. DeAngelo, Naval Daver
Journal: Blood (2021)
Germline breast cancer susceptibility genes, tumor characteristics, and survival
Authors: Peh Joo Ho, Alexis J. Khng, Hui Wen Loh, Weang-Kee Ho, Cheng Har Yip, Nur Aishah Mohd-Taib, Veronique Kiak Mien Tan, Benita Kiat-Tee Tan, Su-Ming Tan, Ern Yu Tan, Swee Ho Lim, Suniza Jamaris, Yirong Sim, Fuh Yong Wong, Joanne Ngeow, Elaine Hsuen Lim, Mei Chee Tai, Eldarina Azfar Wijaya, Soo Chin Lee, Ching Wan Chan, Shaik Ahmad Buhari, Patrick M. Y. Chan, Juliana J. C. Chen, Jaime Chin Mui Seah, Wai Peng Lee, Chi Wei Mok, Geok Hoon Lim, Evan Woo, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Alison M. Dunning, Douglas F. Easton, Marjanka K. Schmidt, Soo-Hwang Teo, Jingmei Li, Mikael Hartman
Journal: Genome Medicine (2021)

Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]). PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.
Abstract P317: Cardiac Fibroblast GSK3α Promotes Myocardial Fibrotic Remodeling Through GSK3α-ERK-IL11 Signaling Circuit
Authors: Prachi Umbarkar, Sultan Tousif, Anand P Singh, Joshua C Anderson, qinkun zhang, Hind Lal
Journal: Circulation Research (2021)

Background: Myocardial fibrosis contributes significantly to heart failure (HF). Fibroblasts are among the predominant cell type in the heart and are primary drivers of fibrosis. To identify the kinases involved in fibrosis, we analyzed the kinome of mouse cardiac fibroblasts (CF) isolated from normal and failing hearts. This unbiased screening revealed the critical role of the GSK-3 family-centric pathways in fibrosis. Previously we have shown that among two isoforms of GSK3, CF-GSK3β acts as a negative regulator of fibrosis in the injured heart. However, the role of CF-GSK3α in the pathogenesis of cardiac diseases is completely unknown. Methods and Results: To define the role of CF-GSK3α in HF, we employed two novel fibroblast-specific KO mouse models. Specifically, GSK3α was deleted from fibroblasts or myofibroblasts with tamoxifen-inducible Tcf21- or periostin- promoter-driven Cre recombinase. In both models, GSK3α deletion restricted pressure overload-induced cardiac fibrosis and preserved cardiac function. We examined the effect of GSK3α deletion on myofibroblast transformation and pro-fibrotic TGFβ1-SMAD3 signaling in vitro . A significant reduction in cell migration, collagen gel contraction, and α-SMA expression in TGFβ1-treated KO CFs confirmed that GSK3α is required for myofibroblast transformation. Surprisingly, GSK3α deletion did not affect SMAD3 activation, indicating the pro-fibrotic role of GSK3α is SMAD3 independent. To further delineate the underlying mechanisms, proteins were isolated from CFs of WT and KO mice at 4 weeks post-injury, and kinome profiling was performed. The kinome analysis identified the downregulation of RAF family kinase activity in KO CFs. Moreover, mapping of significantly altered kinases against literature annotated interactions generated ERK-centric networks. Consistently, flow cytometric analysis of CFs confirmed significantly low levels of pERK in KO mice. Additionally, our in vitro studies demonstrated that GSK3α deletion prevents TGFβ1-induced ERK activation. Interestingly, IL-11, a pro-fibrotic downstream effector of TGFβ1, was remarkably reduced in KO CFs and ERK inhibition further decreased IL-11 expression. Taken together, herein, we discovered the GSK3α-ERK-IL-11 signaling as a critical pro-fibrotic pathway in the heart. Strategies to inhibit this pro-fibrotic network could prevent adverse fibrosis and HF. Conclusion: CF-GSK3α plays a causal role in myocardial fibrosis that could be therapeutically targeted for future clinical applications.
NIMG-66. USING 68GA-DOTATATE PET FOR POSTOPERATIVE GAMMA KNIFE RADIOSURGERY PLANNING IN PATIENTS WITH MENINGIOMA
Authors: David Park, Daniel Ma, Anuj Goenka, Michael Schulder
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Patients with meningiomas are typically treated with maximal safe surgical resection. After subtotal resection or at the time of tumor recurrence, stereotactic radiosurgery (SRS) is often used as the treatment of choice. While magnetic resonance imaging (MRI) is typically used for SRS target delineation, differentiating tumor growth from postoperative change can be challenging. 68Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2 (SSTR2), has been shown to be a reliable biomarker of meningiomas. METHODS We present a consecutive case series of 13 patients with pathology-proven meningioma who received a 68Ga-DOTATATE PET prior to SRS between April 2019 and April 2021. Treatment planning was done at first using MRI only. The DOTATATE-PET images were then used to assess the accurate identification of tumor. RESULTS Ten of the patients had WHO grade 2 meningioma and three patients had WHO grade 1 tumor. Nine patients had recurrent meningiomas and four patients had newly diagnosed disease. Overall, the 68Ga-DOTATATE PET scan revealed additional tumor beyond what was seen on MRI in 5/13 patients. The SRS plan was changed to intensity-modulated radiation therapy (IMRT) for three patients and to octreotide injection in one patient. In one patient, after 68Ga-DOTATATE PET identified previously unrecognized recurrent meningioma in the resection cavity, SRS was performed. In three others, questionable tumor recurrence was seen on MRI, and then confirmed on 68Ga-DOTATATE-PET, but patient observation only was continued due to the small lesion size. CONCLUSION Incorporation of 68Ga-DOTATATE PET data changed SRS treatment in 5/13 our patients with meningioma after prior surgery. We have made this a routine part of our treatment planning and we recommend this method to optimize the use of SRS or RT in these patients. Further data collection is ongoing.
TAMI-22. SEGMENTATION OF DISTINCT TUMOR HALLMARKS OF GLIOBLASTOMA ON DIGITAL HISTOPATHOLOGY USING A HIERARCHICAL DEEP LEARNING APPROACH
Authors: Alvaro Sandino, Ruchika Verma, Yijiang Chen, David Becerra, Eduardo Romero, Pallavi Tiwari
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Glioblastoma is a highly heterogeneous brain tumor. Primary treatment for glioblastoma involves maximally-safe surgical resection. After surgery, resected tissue slides are visually analyzed by neuro-pathologists to identify distinct histological hallmarks characterizing glioblastoma including high cellularity, necrosis, and vascular proliferation. In this work, we present a hierarchical deep learning-based strategy to automatically segment distinct Glioblastoma niches including necrosis, cellular tumor, and hyperplastic blood vessels, on digitized histopathology slides. METHODS We employed the IvyGap cohort for which Hematoxylin and eosin (H&amp;E) slides (digitized at 20X magnification) from n=41 glioblastoma patients were available. Additionally, expert-driven segmentations of cellular tumor, necrosis, and hyperplastic blood vessels (along with other histological attributes) were made available. We randomly employed n=120 slides from 29 patients for training, n=38 slides from 6 cases for validation, and n=30 slides from 6 patients to feed our deep learning model based on Residual Network architecture (ResNet-50). ~2,000 patches of 224x224 pixels were sampled for every slide. Our hierarchical model included first segmenting necrosis from non-necrotic (i.e. cellular tumor) regions, and then from the regions segmented as non-necrotic, identifying hyperplastic blood-vessels from the rest of the cellular tumor. RESULTS Our model achieved a training accuracy of 94%, and a testing accuracy of 88% with an area under the curve (AUC) of 92% in distinguishing necrosis from non-necrotic (i.e. cellular tumor) regions. Similarly, we obtained a training accuracy of 78%, and a testing accuracy of 87% (with an AUC of 94%) in identifying hyperplastic blood vessels from the rest of the cellular tumor. CONCLUSION We developed a reliable hierarchical segmentation model for automatic segmentation of necrotic, cellular tumor, and hyperplastic blood vessels on digitized H&amp;E-stained Glioblastoma tissue images. Future work will involve extension of our model for segmentation of pseudopalisading patterns and microvascular proliferation.
Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults with Ph-like ALL
Authors: Ibrahim Aldoss, Dongyun Yang, Zhaohui Gu, Vanina Tomazian, Sally Mokhtari, Ryan Jackson, Milhan Telatar, Hooi Yew, Monzr M. Al Malki, Amandeep Salhotra, Samer Khaled, Haris Ali, Ahmed Aribi, Karamjeet S. Sandhu, Matthew Mei, Shukaib Arslan, Paul Koller, Andrew S. Artz, Patricia Aoun, Dongqing Gu, David S Snyder, F. Mark Stewart, Peter T. Curtin, Anthony S. Stein, Raju Pillai, Guido Marcucci, Stephen J Forman, Vinod A. Pullarkat, Ryotaro Nakamura, Michelle Afkhami
Journal: Blood (2021)
IMMU-53. STING-ING GLIOBLASTOMA WITH SPHERICAL NUCLEIC ACIDS
Authors: Akanksha Mahajan, Lisa Hurley, Serena Tommasini-Ghelfi, Corey Dussold, Alexander Stegh, Chad Mirkin
Journal: Neuro-Oncology (2021)

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.