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Novel TLR2-binding adjuvant induces enhanced T cell responses and tumor eradication

Ligands for the Toll-like receptor (TLR) family can induce activation of cells of the innate immune system and are widely studied for their potential to enhance adaptive immunity. Conjugation of TLR2-ligand Pa...

Authors: Gijs G. Zom, Marian M. J. H. P. Willems, Selina Khan, Tetje C. van der Sluis, Jan Willem Kleinovink, Marcel G. M. Camps, Gijsbert A. van der Marel, Dmitri V. Filippov, Cornelis J. M. Melief and Ferry Ossendorp

Cryotherapy for nodal metastasis in NSCLC with acquired resistance to immunotherapy

Novel approaches with checkpoint inhibitors in immunotherapy continue to be essential in the treatment of non-small cell lung cancer (NSCLC). However, the low rate of primary response and the development of ac...

Authors: Lucas C. Adam, Junaid Raja, Johannes M. Ludwig, Adebowale Adeniran, Scott N. Gettinger and Hyun S. Kim

Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1⁺ regulatory B cell expansion

Regulatory B (Breg) cells represent one of the B cell subsets that infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, the phenotype, function and clinical re...

Authors: Linsen Ye, Qi Zhang, Yusheng Cheng, Xiaolong Chen, Guoying Wang, Mengchen Shi, Tong Zhang, Yingjiao Cao, Hang Pan, Liting Zhang, Genshu Wang, Yinan Deng, Yang Yang and Guihua Chen

A novel spontaneous hepatocellular carcinoma mouse model for studying T-cell exhaustion in the tumor microenvironment

Immunotherapy has ushered in a new era of cancer therapy, and this is also applicable to therapy of hepatocellular carcinoma (HCC). In this context, effective development of therapeutic strategies requires an ...

Authors: Yu-Tzu Liu, Tai-Chung Tseng, Ruey-Shyang Soong, Chun-Yi Peng, Yu-Hsing Cheng, Shiu-Feng Huang, Tsung-Hsien Chuang, Jia-Horng Kao and Li-Rung Huang

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018): Late-Breaking Abstracts

Authors:

Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: a multi-center study

Immune-mediated diarrhea and colitis (IMDC) can limit immune checkpoint inhibitors (ICIs) treatment, which is efficacious for advanced malignancies. Steroids and infliximab are commonly used to treat it. These...

Authors: Hamzah Abu-Sbeih, Faisal S. Ali, Dana Alsaadi, Joseph Jennings, Wenyi Luo, Zimu Gong, David M. Richards, Aline Charabaty and Yinghong Wang

Treatment duration with immune-based therapies in Cancer: an enigma

Unlike chemotherapy treatments that target the tumor itself (rather nonspecifically), immune-based therapies attempt to harness the power of an individual patient’s immune system to combat cancer. Similar to c...

Authors: Shanta Bantia and Nirmal Choradia

Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations

Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and ...

Authors: Fatima Karzai, David VanderWeele, Ravi A. Madan, Helen Owens, Lisa M. Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L. Beshiri, Kathleen Kelly, Venkatesh Krishnasamy, Sunmin Lee, Min-Jung Lee, Akira Yuno, Jane B. Trepel…

Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance

Chimeric Antigen Receptor (CAR) T cell therapies – adoptive T cell therapies that have been genetically engineered for a new antigen-specificity - have displayed significant success in treating patients with h...

Authors: Michael M. Boyiadzis, Madhav V. Dhodapkar, Renier J. Brentjens, James N. Kochenderfer, Sattva S. Neelapu, Marcela V. Maus, David L. Porter, David G. Maloney, Stephan A. Grupp, Crystal L. Mackall, Carl H. June and Michael R. Bishop

Purinergic targeting enhances immunotherapy of CD73⁺ solid tumors with piggyBac-engineered chimeric antigen receptor natural killer cells

The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an...

Authors: Jiao Wang, Kyle B. Lupo, Andrea M. Chambers and Sandro Matosevic

Oncolytic virus immunotherapy: future prospects for oncology

Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerg...

Authors: Junaid Raja, Johannes M. Ludwig, Scott N. Gettinger, Kurt A. Schalper and Hyun S. Kim

SITC 2018 workshop report: Immuno-Oncology Biomarkers: State of the Art

Identification of biomarkers in cancer immunotherapy that predict therapeutic response and/or limit adverse events are a critical need in the field. To address recent progress and hurdles around cancer biomark...

Authors: Lisa H. Butterfield, Mary L. Disis, Bernard A. Fox, David R. Kaufman, Samir N. Khleif and Ena Wang

Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients

A high density of tumor-infiltrating CD8⁺ T cells and CD20⁺ B cells correlates with prolonged survival in patients with a wide variety of human cancers, including high-grade serous ovarian carcinoma (HGSC). Howev...

Authors: Iva Truxova, Lenka Kasikova, Michal Hensler, Petr Skapa, Jan Laco, Ladislav Pecen, Lucie Belicova, Ivan Praznovec, Michael J. Halaska, Tomas Brtnicky, Eva Salkova, Lukas Rob, Roman Kodet, Jeremy Goc, Catherine Sautes-Fridman, Wolf Herman Fridman…

Which is the optimal immunotherapy for advanced squamous non-small-cell lung cancer in combination with chemotherapy: anti-PD-1 or anti-PD-L1?

Recent randomized phase III trials (KEYNOTE-407 and IMpower131) reported that adding anti-programmed death (ligand) 1 (anti-PD-(L)1) antibodies in combination with taxane-platinum improve the therapeutic effic...

Authors: Yaxiong Zhang, Huaqiang Zhou and Li Zhang

Immunotherapy utilizing the combination of natural killer– and antibody dependent cellular cytotoxicity (ADCC)–mediating agents with poly (ADP-ribose) polymerase (PARP) inhibition

Poly (ADP-ribose) polymerase inhibitors (PARPi) prevent single-stranded DNA repair. Olaparib is a PARPi approved for the treatment of BRCA mutant ovarian and breast carcinoma. Emerging clinical data suggest a ...

Authors: Kathleen E. Fenerty, Michelle Padget, Benjamin Wolfson, Sofia R. Gameiro, Zhen Su, John H. Lee, Shahrooz Rabizadeh, Patrick Soon-Shiong and James W. Hodge

Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results

AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results ...

Authors: Jacek Mackiewicz, Tomasz Burzykowski, Dariusz Iżycki and Andrzej Mackiewicz

Soluble immune checkpoints in cancer: production, function and biological significance

Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer. Based on this, monoclonal antibodies are h...

Authors: Daqian Gu, Xiang Ao, Yu Yang, Zhuo Chen and Xiang Xu

Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy

Merkel cell carcinoma (MCC) is an aggressive skin cancer that frequently responds to anti-PD-1 therapy. MCC is associated with sun exposure and, in 80% of cases, Merkel cell polyomavirus (MCPyV). MCPyV-specifi...

Authors: Natalie J. Miller, Candice D. Church, Steven P. Fling, Rima Kulikauskas, Nirasha Ramchurren, Michi M. Shinohara, Harriet M. Kluger, Shailender Bhatia, Lisa Lundgren, Martin A. Cheever, Suzanne L. Topalian and Paul Nghiem

Atypical response with bone pseudoprogression in a patient receiving nivolumab for advanced cutaneous squamous cell carcinoma

Currently, there is no established standard of care for patients with metastatic CSCC. Based on the mechanisms of CSCC carcinogenesis has been postulated that these tumors may be amenable to PD-1/PD-L1 blockade.

Authors: Leandro J. C. Oliveira, Aline B. L. Gongora, Felipe G. Barbosa, Carlos H. dos Anjos and Rodrigo R. Munhoz

Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies

Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lu...

Authors: Aixa E. Soyano, Bhagirathbhai Dholaria, Julian A. Marin-Acevedo, Nancy Diehl, David Hodge, Yan Luo, Rami Manochakian, Saranya Chumsri, Alex Adjei, Keith L. Knutson and Yanyan Lou

A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors

Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inh...

Authors: Vivek Verma, Tanja Sprave, Waqar Haque, Charles B. Simone II, Joe Y. Chang, James W. Welsh and Charles R. Thomas Jr

Lipid nanoparticles that deliver IL-12 messenger RNA suppress tumorigenesis in MYC oncogene-driven hepatocellular carcinoma

Interleukin-12 (IL-12) is a promising candidate for cancer immunotherapy because of its ability to activate a number of host immune subsets that recognize and destroy cancer cells. We found that human hepatoce...

Authors: Ian Lai, Srividya Swaminathan, Virginie Baylot, Adriane Mosley, Renumathy Dhanasekaran, Meital Gabay and Dean W. Felsher

Resistance to anti-PD-1-based immunotherapy in basal cell carcinoma: a case report and review of the literature

Immunotherapy with immune checkpoint inhibitors has radically changed the management of a broad spectrum of tumors. In contrast, only very limited information is available about the efficacy of these therapies...

Authors: Francesco Sabbatino, Antonio Marra, Luigi Liguori, Giosuè Scognamiglio, Celeste Fusciello, Gerardo Botti, Soldano Ferrone and Stefano Pepe

Acquired resistance to immunotherapy in MMR-D pancreatic cancer

MMR-D pancreatic cancer have been reported to respond to checkpoint inhibitor therapy. Here, we report the first case of acquired resistance to immunotherapy in MMR-D pancreatic cancer.

Authors: Zishuo Ian Hu, Matthew D. Hellmann, Jedd D. Wolchok, Monika Vyas, Jinru Shia, Zsofia K. Stadler, Luis A. Diaz Jr and Eileen M. O’Reilly

Cost-effectiveness of nivolumab plus ipilimumab as first-line therapy in advanced renal-cell carcinoma

Nivolumab plus ipilimumab improves overall survival and is associated with less toxicity compared with sunitinib in the first-line setting of advanced renal-cell carcinoma (RCC). The current study aimed to ass...

Authors: Bin Wu, Qiang Zhang and Jie Sun

RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer

T lymphocytes and HLA expression on tumor cell both influence prognostic of localized colorectal cancer, but their role following chemotherapy in patients with liver metastatic colorectal cancer (mCRC) was not...

Authors: Fanny Ledys, Quentin Klopfenstein, Caroline Truntzer, Laurent Arnould, Julie Vincent, Leila Bengrine, Romain Remark, Romain Boidot, Sylvain Ladoire, Francois Ghiringhelli and Valentin Derangere

Kaposi’s varicelliform eruption in a patient with metastatic melanoma and primary cutaneous anaplastic large cell lymphoma treated with talimogene laherparepvec and nivolumab

Immune-directed therapies have become front-line therapy for melanoma and are transforming the management of advanced disease. In refractory cases, multi-modal immunoncology (IO) approaches are being utilized,...

Authors: David M. Miller, Ryan M. Trowbridge, Anupam Desai and Reed E. Drews

Immunoregulatory functions of innate lymphoid cells

Innate lymphoid cells (ILCs) are increasingly being recognized for their ability to impact both innate and adaptive immune cells in diverse contexts. ILCs have been observed in all secondary lymphoid tissues, ...

Authors: Sarah Q. Crome and Pamela S. Ohashi

STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial

The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumo...

Authors: Matthew J. Reilley, Patricia McCoon, Carl Cook, Paul Lyne, Razelle Kurzrock, Youngsoo Kim, Richard Woessner, Anas Younes, John Nemunaitis, Nathan Fowler, Michael Curran, Qinying Liu, Tianyuan Zhou, Joanna Schmidt, Minji Jo, Samantha J. Lee…

Immune checkpoint inhibitor-related acral vasculitis

Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resec...

Authors: Thibault Comont, Vincent Sibaud, Loïc Mourey, Pierre Cougoul and Odile Beyne-Rauzy

Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer

The pancreatic cancer vaccine, GVAX, induces novel lymphoid aggregates in the otherwise immune quiescent pancreatic ductal adenocarcinoma (PDAC). GVAX also upregulates the PD-1/PD-L1 pathway, and a pre-clinica...

Authors: May Tun Saung, Stephen Muth, Ding Ding, Dwayne L. Thomas II, Alex B. Blair, Takahiro Tsujikawa, Lisa Coussens, Elizabeth M. Jaffee and Lei Zheng

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018)

Authors:

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018)

Authors:

CD33/CD3-bispecific T-cell engaging (BiTE®) antibody construct targets monocytic AML myeloid-derived suppressor cells

Acute myeloid leukemia (AML) is the most common acute leukemia amongst adults with a 5-year overall survival lower than 30%. Emerging evidence suggest that immune alterations favor leukemogenesis and/or AML re...

Authors: Regina Jitschin, Domenica Saul, Martina Braun, Sehmus Tohumeken, Simon Völkl, Roman Kischel, Michael Lutteropp, Cedric Dos Santos, Andreas Mackensen and Dimitrios Mougiakakos

Paraneoplastic hyperleucocytosis in a melanoma patient after initiation of ipilimumab and nivolumab combination therapy

Paraneoplastic hyperleucocytosis (PH) is sporadically seen in patients with advanced solid tumors.

Authors: Thilo Gambichler, E. Stockfleth and L. Susok

Neoadjuvant ipilimumab (3 mg/kg or 10 mg/kg) and high dose IFN-α2b in locally/regionally advanced melanoma: safety, efficacy and impact on T-cell repertoire

Neoadjuvant immunotherapy utilizing novel combinations has the potential to transform the standard of care for locally/regionally advanced melanoma. We hypothesized that neoadjuvant ipilimumab in combination w...

Authors: Ahmad Tarhini, Yan Lin, Huang Lin, Zahra Rahman, Priyanka Vallabhaneni, Prateek Mendiratta, James F. Pingpank, Matthew P. Holtzman, Erik C. Yusko, Julie A. Rytlewski, Uma N. M. Rao, Robert L. Ferris and John M. Kirkwood

Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial

We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC).

Authors: Christophe Le Tourneau, Christopher Hoimes, Corrine Zarwan, Deborah J. Wong, Sebastian Bauer, Rainer Claus, Martin Wermke, Subramanian Hariharan, Anja von Heydebreck, Vijay Kasturi, Vikram Chand and James L. Gulley

Safety and efficacy of nivolumab in combination with sunitinib or pazopanib in advanced or metastatic renal cell carcinoma: the CheckMate 016 study

Combination treatment with immune checkpoint inhibitors and antiangiogenic drugs has shown encouraging preliminary antitumor activity across various tumor types including advanced or metastatic renal cell carc...

Authors: Asim Amin, Elizabeth R Plimack, Marc S Ernstoff, Lionel D Lewis, Todd M Bauer, David F McDermott, Michael Carducci, Christian Kollmannsberger, Brian I Rini, Daniel Y C Heng, Jennifer Knox, Martin H Voss, Jennifer Spratlin, Elmer Berghorn, Lingfeng Yang and Hans J Hammers

A severe case of neuro-Sjögren’s syndrome induced by pembrolizumab

The prevalence of connective tissue disease (CTD) induced by immune checkpoint inhibitors (CPIs) in the absence of pre-existing autoimmunity is unknown.

Authors: Jaqueline Ghosn, Alex Vicino, Olivier Michielin, George Coukos, Thierry Kuntzer and Michel Obeid

Trial Reporting in Immuno-Oncology (TRIO): An American Society of Clinical Oncology-Society for Immunotherapy of Cancer Statement

To develop recommendations for clinical trial reporting that address the unique efficacy, toxicity, and combination and sequencing aspects of immuno-oncology (IO) treatments.

Authors: Apostolia M. Tsimberidou, Laura A. Levit, Richard L. Schilsky, Steven D. Averbuch, Daniel Chen, John M. Kirkwood, Lisa M. McShane, Elad Sharon, Kathryn F. Mileham and Michael A. Postow

Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab

Nivolumab is approved for the treatment of refractory metastatic renal cell carcinoma. Patterns and predictors of progressive disease (PD) on nivolumab, and outcomes in such patients are lacking.

Authors: Haris Zahoor, Pedro C. Barata, Xuefei Jia, Allison Martin, Kimberly D. Allman, Laura S. Wood, Timothy D. Gilligan, Petros Grivas, Moshe C. Ornstein, Jorge A. Garcia and Brian I. Rini

Targeting VEGFR2 with Ramucirumab strongly impacts effector/ activated regulatory T cells and CD8⁺ T cells in the tumor microenvironment

Several studies have established a correlation between the VEGF–VEGFR2 axis and an immunosuppressive microenvironment; this immunosuppression can be overcome by anti-angiogenic reagents, such as ramucirumab (R...

Authors: Yasuko Tada, Yosuke Togashi, Daisuke Kotani, Takeshi Kuwata, Eichi Sato, Akihito Kawazoe, Toshihiko Doi, Hisashi Wada, Hiroyoshi Nishikawa and Kohei Shitara

Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series

The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events a...

Authors: Kendall F. Moseley, Jarushka Naidoo, Clifton O. Bingham, Michael A. Carducci, Patrick M. Forde, Geoffrey T. Gibney, Evan J. Lipson, Ami A. Shah, William H. Sharfman and Laura C. Cappelli

Fluorine-19 MRI for detection and quantification of immune cell therapy for cancer

Over the past two decades, immune cell therapy has emerged as a potent treatment for multiple cancers, first through groundbreaking leukemia therapy, and more recently, by tackling solid tumors. Developing suc...

Authors: Fanny Chapelin, Christian M Capitini and Eric T Ahrens

Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis

Immune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have significant side e...

Authors: Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Junsheng Ma, Roland L Bassett Jr, Noha Abdel-Wahab, Jaime Anderson, Jennifer E Davis, Jocelyn Joseph, Marc Uemura, Ali Noman, Hamzah Abu-Sbeih, Cassian Yee, Rodabe Amaria, Sapna Patel, Hussein Tawbi…

A nomogram-based immunoprofile predicts overall survival for previously untreated patients with esophageal squamous cell carcinoma after esophagectomy

Immunoscore, as a prognostic tool defined to quantify in situ immune cell infiltrates, appears to be superior to the TNM staging system. In esophageal squamous cell carcinoma (ESCC), no immunoscore has been es...

Authors: Jingjing Duan, Yongwei Xie, Lijuan Qu, Lingxiong Wang, Shunkai Zhou, Yu Wang, Zhongyi Fan, Shengsheng Yang and Shunchang Jiao

Serious adverse events and fatal adverse events associated with nivolumab treatment in cancer patients

Nivolumab, an immune checkpoint inhibitor, has revolutionized the treatment of many cancers. Due to its novel mechanisms of action, nivolumab induces a distinct profile of adverse events. Currently, the incide...

Authors: Bin Zhao, Hong Zhao and Jiaxin Zhao

Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option

The treatment of metastatic melanoma patients with autologous tumor-infiltrating lymphocytes (TIL) shows robust, reproducible, clinical responses in clinical trials executed in several specialized centers over...

Authors: Maartje W. Rohaan, Joost H. van den Berg, Pia Kvistborg and John B. A. G. Haanen

Ibuprofen supports macrophage differentiation, T cell recruitment, and tumor suppression in a model of postpartum breast cancer

Women diagnosed with breast cancer within 5 years postpartum (PPBC) have poorer prognosis than age matched nulliparous women, even after controlling for clinical variables known to impact disease outcomes. Thr...

Authors: Nathan D. Pennock, Holly A. Martinson, Qiuchen Guo, Courtney B. Betts, Sonali Jindal, Takahiro Tsujikawa, Lisa M. Coussens, Virginia F. Borges and Pepper Schedin

Durable response to anti-PD-1 immunotherapy in epithelioid angiomyolipoma: a report on the successful treatment of a rare malignancy

Malignant angiomyolipoma is an uncommon tumor of the class of perivasciular epithelioid cell neoplasms (PEComas). These tumors are characteristically driven by deleterious mutations in the tumor suppressors TSC1 ...

Authors: Michael Lattanzi, Fang-Ming Deng, Luis A. Chiriboga, Alisa N. Femia, Shane A. Meehan, Gopa Iyer, Martin H. Voss, Yuliya Sundatova, William C. Huang and Arjun V. Balar