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Cancer Immunology Research

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https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#1
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including Programmed death-ligand 1 (PD-L1) and its receptor Programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers.  Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma.  However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood.  We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
May 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28515123/all-trans-retinoic-acid-prevents-osteosarcoma-metastasis-by-inhibiting-m2-polarization-of-tumor-associated-macrophages
#2
Qian Zhou, Miao Xian, Senfeng Xiang, Danyan Xiang, Xuejing Shao, Jincheng Wang, Ji Cao, Xiaochun Yang, Bo Yang, Meidan Ying, Qiaojun He
M2-polarized tumor associated macrophages (TAM) play a critical role in cancer invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis of K7M2 WT osteosarcoma cells to the lung in mice, thus establishing M2 TAMs as a therapeutic target for blocking osteosarcoma metastasis. We found that all-trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the M2 polarization of TAMs. ATRA suppressed IL13 or IL4 induced M2-type macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2-type macrophages in vitro ATRA reduced the number of pulmonary metastatic nodes of osteosarcoma and decreased expression of M2-type macrophages in metastatic nodes both in intravenous injection and orthotopic transplantation models...
May 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28483787/a-sting-agonist-given-with-ox40-receptor-and-pd-l1-modulators-primes-immunity-and-reduces-tumor-growth-in-tolerized-mice
#3
Jeremy B Foote, Marleen Kok, James M Leatherman, Todd D Armstrong, Bridget C Marcinkowski, Laureen S Ojalvo, David B Kanne, Elizabeth M Jaffee, Thomas W Dubensky, Leisha A Emens
STING signaling induces interferon-β (IFNβ) production by intratumoral dendritic cells (DCs), driving T-cell priming and recruitment into the tumor microenvironment (TME). We examined to what extent pre-existing antigen tolerance influenced the efficacy of in situ delivery of a potent STING-activating cyclic dinucleotide (CDN), ADU S-100, against established HER-2(+) breast tumors. ADU S-100 induced HER-2-specific CD8(+) T-cell priming and durable tumor clearance in 100% of nontolerant parental FVB/N mice...
May 8, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28473315/4-1bb-enhanced-expansion-of-cd8-til-from-triple-negative-breast-cancer-unveils-mutation-specific-cd8-t-cells
#4
Michiko Harao, Marie-Andrée Forget, Jason Roszik, Hui Gao, Gildy V Babiera, Savitri Krishnamurthy, Jessica A Chacon, Shumin Li, Elizabeth A Mittendorf, Sarah M DeSnyder, Korrene F Rockwood, Chantale Bernatchez, Naoto T Ueno, Laszlo G Radvanyi, Luis Vence, Cara Haymaker, James M Reuben
Triple negative breast cancer (TNBC) highly infiltrated with CD8(+) tumor-infiltrating lymphocytes (TILs) has been associated with improved prognosis. This observation led us to hypothesize that CD8(+) TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8(+) TILs in solid cancers other than melanoma. To overcome this obstacle, we used an agonistic antibody  (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8(+) T cells...
May 4, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28473314/combined-anti-vegf-and-anti-ctla-4-therapy-elicits-humoral-immunity-to-galectin-1-which-is-associated-with-favorable-clinical-outcomes
#5
Xinqi Wu, Jingjing Li, Erin M Connolly, Xiaoyun Liao, Jing Ouyang, Anita Giobbie-Hurder, Donald Lawrence, David McDermott, George Murphy, Jun Zhou, Matthias Piesche, Glenn Dranoff, Scott Rodig, Margaret Shipp, F Stephen Hodi
The combination of anti-VEGF blockade (bevacizumab) with immune checkpoint anti-CTLA-4 blockade (ipilimumab) in a phase I study showed tumor endothelial activation and immune cell infiltration that were associated with favorable clinical outcomes in patients with metastatic melanoma. To identify potential immune targets responsible for these observations, post-treatment plasma from long-term responding patients were used to screen human protein arrays. We reported that ipilimumab plus bevacizumab therapy elicited humoral immune responses to galectin-1 (Gal-1) which exhibits pro-tumor, pro-angiogenesis, and immunosuppressive activities in 37...
May 4, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468916/tumor-derived-%C3%AE-fetoprotein-directly-drives-human-natural-killer-cell-activation-and-subsequent-cell-death
#6
Lazar Vujanovic, Elizabeth C Stahl, Angela D Pardee, David A Geller, Allan Tsung, Simon C Watkins, Gregory A Gibson, Walter J Storkus, Lisa H Butterfield
Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK) cell numbers and function have been shown to have a poor disease outcome. Mechanisms underlying NK cell deficiency and dysfunction in HCC patients remain largely unresolved. a-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair NK cell activity by suppressing dendritic cell function. However, a direct tAFP effect on NK cells remains unexplored. The purpose of this study was to examine the ability of cord blood-derived AFP (nAFP) and that of tAFP to directly modulate human NK cell activity and longevity in vitro Short-term exposure to tAFP and, especially, nAFP proteins induced a unique pro-inflammatory, IL2-hyperresponsive phenotype in NK cells as measured by IL1β, IL6, and TNF secretion, CD69 upregulation, and enhanced tumor cell killing...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468915/combining-dna-vaccine-and-aida-1-in-attenuated-salmonella-activates-tumor-specific-cd4-and-cd8-t-cell-responses
#7
Yu Mei, Lixiang Zhao, Yonghao Liu, Huanle Gong, Yuan Song, Lei Lei, Ying Zhu, Ziqi Jin, Shoubao Ma, Bo Hu, Qing Sun, Haiyan Liu
Stimulation of tumor-specific responses in both CD4(+) and CD8(+) T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4(+) and CD8(+) T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468914/rig-i-resists-hypoxia-induced-immunosuppression-and-dedifferentiation
#8
Christina Engel, Grethe Brügmann, Silke Lambing, Larissa H Mühlenbeck, Samira Marx, Christian Hagen, Dorottya Horváth, Marion Goldeck, Janos Ludwig, Anna-Maria Herzner, Jan W Drijfhout, Daniela Wenzel, Christoph Coch, Thomas Tüting, Martin Schlee, Veit Hornung, Gunther Hartmann, Jasper G Van den Boorn
A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I interferon (IFN), chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28411193/liver-metastasis-and-treatment-outcome-with-anti-pd-1-monoclonal-antibody-in-patients-with-melanoma-and-nsclc
#9
Paul C Tumeh, Matthew D Hellmann, Omid Hamid, Katy K Tsai, Kimberly L Loo, Matthew A Gubens, Michael Rosenblum, Christina L Harview, Janis M Taube, Nathan Handley, Neharika Khurana, Adi Nosrati, Matthew F Krummel, Andrew Tucker, Eduardo V Sosa, Phillip J Sanchez, Nooriel Banayan, Juan C Osorio, Dan L Nguyen-Kim, Jeremy Chang, I Peter Shintaku, Peter D Boasberg, Emma J Taylor, Pamela N Munster, Alain P Algazi, Bartosz Chmielowski, Reinhard Dummer, Tristan R Grogan, David Elashoff, Jimmy Hwang, Simone M Goldinger, Edward B Garon, Robert H Pierce, Adil Daud
We explored the association between liver metastases, tumor CD8(+) T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30...
April 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28385737/lack-of-stat6-attenuates-inflammation-and-drives-protection-against-early-steps-of-colitis-associated-colon-cancer
#10
Sonia A Leon-Cabrera, Emmanuel Molina-Guzman, Yael G Delgado-Ramirez, Armando Vázquez-Sandoval, Yadira Ledesma-Soto, Carlos G Pérez-Plasencia, Yolanda I Chirino, Norma L Delgado-Buenrostro, Miriam Rodríguez-Sosa, Felipe Vaca-Paniagua, Federico Ávila-Moreno, Emma B Gutierrez-Cirlos, Luis E Arias-Romero, Luis I Terrazas
Colitis-associated colon cancer (CAC) is one of the most common malignant neoplasms and a leading cause of death. The immunologic factors associated with CAC development are not completely understood. Signal transducer and activator of transcription 6 (STAT6) is part of an important signaling pathway for modulating intestinal immune function and homeostasis. However, the role of STAT6 in colon cancer progression is unclear. Following CAC induction in wild-type (WT) and STAT6-deficient mice (STAT6(-/-)), we found that 70% of STAT6(-/-) mice were tumor-free after 8 weeks, whereas 100% of WT mice developed tumors...
April 6, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28351891/squamous-cell-tumors-recruit-%C3%AE-%C3%AE-t-cells-producing-either-il17-or-ifn%C3%AE-depending-on-the-tumor-stage
#11
Elena Lo Presti, Francesca Toia, Sebastiano Oieni, Simona Buccheri, Alice Turdo, Laura Rosa Mangiapane, Giuseppina Campisi, Valentina Caputo, Matilde Todaro, Giorgio Stassi, Adriana Cordova, Francesco Moschella, Gaetana Rinaldi, Serena Meraviglia, Francesco Dieli
The identification of reciprocal interactions between tumor-infiltrating immune cells and the microenviroment may help us understand mechanisms of tumor growth inhibition or progression. We have assessed the frequencies of tumor-infiltrating and circulating γδ T cells and regulatory T cells (Treg) from 47 patients with squamous cell carcinoma (SCC), to determine if they correlated with progression or survival. Vδ1 T cells infiltrated SSC tissue to a greater extent than normal skin, but SCC patients and healthy subjects had similar amounts circulating...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28351890/targeting-cd47-and-autophagy-elicited-enhanced-antitumor-effects-in-non-small-cell-lung-cancer
#12
Xuyao Zhang, Jiajun Fan, Shaofei Wang, Yubin Li, Yichen Wang, Song Li, Jingyun Luan, Ziyu Wang, Ping Song, Qicheng Chen, Wenzhi Tian, Dianwen Ju
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in non-small cell lung cancer (NSCLC). SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes...
March 28, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28314751/identification-of-glycopeptides-as-posttranslationally-modified-neoantigens-in-leukemia
#13
Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin C Loke, Manoj Raghavan, Dina L Bai, Jeffrey Shabanowitz, Donald F Hunt, Mark Cobbold
Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues...
March 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28254786/clinical-impact-of-tumor-dna-repair-expression-and-t-cell-infiltration-in-breast-cancers
#14
Andrew R Green, Mohammed A Aleskandarany, Reem Ali, Eleanor Grace Hodgson, Suha Atabani, Karen De Souza, Emad Rakha, Ian O Ellis, Srinivasan Madhusudan
Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1269 breast cancers and validated our findings in an independent estrogen receptor (ER)- cohort (n = 279)...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28465453/rational-combination-immunotherapy-understand-the-biology
#15
Howard L Kaufman
Selecting rational treatment combinations remains a major challenge for improving immunotherapy outcomes. In this issue of Cancer Immunology Research, Zhang and colleagues reduced tumors by inhibiting CD47 in a lung carcinoma model, a treatment that inadvertently induced autophagy through inhibition of the Akt/mTOR pathway. By also targeting autophagy, the therapeutic response improved, highlighting the importance of understanding the biology beneath antitumor immunity. Cancer Immunol Res; 5(5); 355-6. ©2017 AACRSee article by Zhang et al...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28465452/human-tumor-antigens-yesterday-today-and-tomorrow
#16
REVIEW
Olivera J Finn
The question of whether human tumors express antigens that can be recognized by the immune system has been answered with a resounding YES. Most were identified through spontaneous antitumor humoral and cellular immune responses found in cancer patients and include peptides, glycopeptides, phosphopeptides, viral peptides, and peptides resulting from common mutations in oncogenes and tumor-suppressor genes, or common gene fusion events. Many have been extensively tested as candidates for anticancer vaccines. More recently, attention has been focused on the potentially large number of unique tumor antigens, mutated neoantigens, that are the predicted products of the numerous mutations revealed by exome sequencing of primary tumors...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28465451/about-the-master
#17
REVIEW
(no author information available yet)
No abstract text is available yet for this article.
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28465450/what-we-re-reading-article-recommendations-from-our-deputy-and-senior-editors
#18
(no author information available yet)
No abstract text is available yet for this article.
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28408386/increased-pd-1-and-tim-3-tils-during-cetuximab-therapy-inversely-correlate-with-response-in-head-and-neck-cancer-patients
#19
Hyun-Bae Jie, Raghvendra M Srivastava, Athanassios Argiris, Julie E Bauman, Lawrence P Kane, Robert L Ferris
Despite emerging appreciation for the important role of immune checkpoint receptors in regulating the effector functions of T cells, it is unknown whether their expression is involved in determining the clinical outcome in response to cetuximab therapy. We examined the expression patterns of immune checkpoint receptors (including PD-1, CTLA-4, and TIM-3) and cytolytic molecules (including granzyme B and perforin) of CD8(+) tumor-infiltrating lymphocytes (TIL) and compared them with those of peripheral blood T lymphocytes (PBL) in patients with head and neck cancer (HNSCC) during cetuximab therapy...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28396509/clinical-features-of-acquired-resistance-to-anti-pd-1-therapy-in-advanced-melanoma
#20
Daniel Y Wang, Zeynep Eroglu, Alpaslan Ozgun, Paul D Leger, Shilin Zhao, Fei Ye, Jason J Luke, Richard W Joseph, Rizwan Haq, Patrick A Ott, F Stephen Hodi, Jeffrey A Sosman, Douglas B Johnson, Elizabeth I Buchbinder
Anti-PD-1 therapy has improved clinical outcomes in advanced melanoma, but most patients experience intrinsic resistance. Responding patients can develop acquired resistance to anti-PD-1. We retrospectively reviewed 488 patients treated with anti-PD-1 from three academic centers and identified 36 patients with acquired resistance, defined as disease progression following objective response. The incidence, timing, disease sites, post-progression survival (PPS), and outcomes were evaluated descriptively. The acquired resistance cohort consisted of 67% with more than 1 feature of poor prognosis (stage M1c, elevated LDH, or brain metastasis), and 67% had previously received ipilimumab...
May 2017: Cancer Immunology Research
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