scholarly journals The control of acidity in tumor cells: a biophysical model

2020 ◽  
Author(s):  
Nicola Piasentin ◽  
Edoardo Milotti ◽  
Roberto Chignola
Keyword(s):  
Experimental Data ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Biophysical Model ◽  
Tumor Aggressiveness ◽  
Surrounding Environment ◽  
Carbonic Anhydrase 9 ◽  
Independent Experimental Data ◽  
Dynamic Interplay

ABSTRACTAcidosis of the tumor microenvironment leads to cancer invasion, progression and resistance to therapies. We present a biophysical model that describes how tumor cells regulate intracellular and extracellular acidity while they grow in a microenvironment characterized by increasing acidity and hypoxia. The model takes into account the dynamic interplay between glucose and O2 consumption with lactate and CO2 production and connects these processes to H+ and fluxes inside and outside cells. We have validated the model with independent experimental data and used it to investigate how and to which extent tumor cells can survive in adverse micro-environments characterized by acidity and hypoxia. The simulations show a dominance of the H+ exchanges in well-oxygenated regions, and of exchanges in the inner hypoxic regions where tumor cells are known to acquire malignant phenotypes. The model also includes the activity of the enzyme Carbonic Anhydrase 9 (CA9), a known marker of tumor aggressiveness, and the simulations demonstrate that CA9 acts as a nonlinear pHi equalizer at any O2 level in cells that grow in acidic extracellular environments.SIGNIFICANCEThe activity of cancer cells in solid tumors affects the surrounding environment in many ways, and an elevated acidity is a common feature of the tumor microenvironment. In this paper we propose a model of intracellular/extracellular acidity that is linked to cellular metabolism and includes all the main molecular players. The model is reliable, robust and validated with experimental data and can be used as an essential building block of more comprehensive in silico research on solid tumors.

scholarly journals P09.05 Plasma CD27, a surrogate of intratumoral CD27-CD70 interaction, correlates with immunotherapy resistance in renal cancer

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A30.1-A30
Author(s):  
N Benhamouda ◽  
I Sam ◽  
N Epaillard ◽  
A Gey ◽  
A Saldmann ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Principal Investigator ◽  
Cell Phenotype ◽  
Metastatic Rcc ◽  
Research Grant

BackgroundCD70, a costimulatory molecule on antigen presenting cells, is known to activate CD27-expressing T cells. CD27-CD70 interaction leads to the release of soluble CD27 (sCD27). However, persistent interaction of CD27 and CD70 such as in chronic infection may exhaust the T cell pool and promote apoptosis. Surprisingly, our analysis based on TCGA database show that clear cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors. Despite the important clinical efficacy of immunotherapy by anti-PD-1 in RCC patients, the overall response to anti-PD1 remains modest. The relationship between the CD27-CD70 interaction in the RCC and the response to immunotherapy is still unclear.Materials and MethodsTo study the CD27 and CD70 expression in the tumor microenvironment (TME), FFPE tumor tissues from 25 RCC patients were analysed using multiplex in situ immunofluorescence. 10 fresh RCC tumor samples were collected to analyse the phenotype of CD27+ T cells by flow cytometry and 4 samples were proceeded for single-cell RNA-seq analysis. A cohort of metastatic RCC patients (n = 35) treated by anti-PD-1 were enrolled for the measurement of plasma sCD27 by ELISA and the survival analysis is also realized.ResultsIn the TME, we demonstrated that CD27+ T cells interact with CD70-expressing tumor cells. In fresh tumors from RCC patients, CD27+ T cells express higher levels of cleaved caspase 3 (a classical marker of apoptosis) than CD27- T cells. We confirmed the apoptotic signature (BAX, FASLG, BCL2L11, CYCS, FBXO32, LGALS1, PIK3R1, TERF1, TXNIP, CDKN2A) of CD27+ T cells by single-cell RNAseq analysis. CD27+T cells also had a tissue resident memory T cell phenotype with enriched gene expression of ITGAE, PRDM1, RBPJ and ZNF683. Moreover, CD27+T cells display an exhaustion phenotype with the expression of multiple inhibitory receptors gene signature (PDCD1, CTLA4, HAVCR2, LAG3, etc). Besides, intratumoral CD27-CD70 interaction significantly correlates with plasma sCD27 concentration in RCC (p = 0.0017). In metastatic RCC patients treated with anti-PD-1, higher levels of sCD27 predict poor overall survival (p = 0.037), while it did not correlate with inflammatory markers or clinical prognostic criteria.ConclusionsIn conclusion, we demonstrated that sCD27, a surrogate of T cell dysfunction in tumors likely induced by persistent interactions of CD27+T cells and CD70-expressing tumor cells, is a predictive biomarker of resistance to immunotherapy in mRCC. To our knowledge, this is the first report showing that a peripheral blood biomarker may reflect certain aspects of the tumor-host interaction in the tumor microenvironment. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be further extended to other types of tumors. CD70-CD27 interaction could thus be considered as a mechanism of tumor escape, but also a novel therapeutic target in cancers.Disclosure InformationN. Benhamouda: None. I. Sam: None. N. Epaillard: None. A. Gey: None. A. Saldmann: None. J. Pineau: None. M. Hasan: None. V. Verkarre: None. V. Libri: None. S. Mella: None. C. Granier: None. C. Broudin: None. P. Ravel: None. B. Jabla: None. N. Chaput: None. L. Albiges: None. Y. Vano: None. O. Adotevi: None. S. Oudard: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; SIRIC CARPEM, FONCER. E. Tartour: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Modest; Fondation ARC, INCA PLBio, Labex Immuno-Oncology, SIRIC CARPEM, FONCER, IDEX université de Paris, Inserm Transfert.

scholarly journals 799 Neoantigen-cytokine-chemokine multifunctional natural killer cell engager for immunotherapy of solid tumors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A834-A834
Author(s):  
Xue Yao ◽  
Sandro Matosevic
Keyword(s):  
Tumor Microenvironment ◽  
Cell Therapy ◽  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Nk Cell ◽  
Killer Cell ◽  
Nk Cell Therapy

BackgroundThe effectiveness of natural killer (NK) cell-based immunotherapy against solid tumors is limited by the lack of specific antigens and the immunosuppressive tumor microenvironment (TME). Glioblastoma multiforme (GBM) is one such heavily immunosuppressive tumor that has been particularly hard to target and remains without a viable treatment. The development of novel approaches to enhance the efficacy of NK cells against GBM is urgently needed. NK cell engagers (NKCE) have been developed to enhance the efficacy of NK cell therapy.MethodsTo improve the clinical efficacy of NK cell therapy, we are developing a new generation of multi-specific killer engagers, which consists of a neoantigen-targeting moiety, together with cytokine and chemokine-producing domains. Neoantigens are new antigens formed specifically in tumor cells due to genome mutations, making them highly specific tools to target tumor cells. Our engager has been designed to target Wilms' tumor-1 (WT-1), a highly specific antigen overexpressed in GBM among other solid tumors. This is done through the generation of an scFv specific targeting the complex of WT-1126-134/HLA-A*02:01 on the surface of GBM. On the NK cell side, the engager is designed to target the activating receptor NKp46. Incorporation of the cytokine IL-15 within the engager supports the maturation, persistence, and expansion of NK cells in vivo while favoring their proliferation and survival in the tumor microenvironment. Additionally, our data indicated that the chemokine CXCL10 plays an important role in the infiltration of NK cells into GBM, however, GBM tumors produce low levels of this chemokine. Incorporation of a CXCL10-producing function into our engager supports intratumoral NK cell trafficking by promoting, through their synthetic production, increased levels of CXCL10 locally in the tumor microenvironment.ResultsCollectively, this has resulted in a novel multifunctional NK cell engager, combining neoantigen-cytokine-chemokine elements fused to an activating domain-specific to NK cells, and we have investigated its ability to support and enhance NK cell-mediated cytotoxicity against solid tumors in vitro and in vivo against patient-derived GBM models. The multi-specific engager shows both high tumor specificity, as well as the ability to overcome NK cell dysfunction encountered in the GBM TME.ConclusionsWe hypothesize that taking advantage of our multi-functional engager, NK cells will exhibit superior ex vivo expansion, infiltration, and antitumor activity in the treatment of GBM and other solid tumors.

A biomimetic nanozyme/camptothecin hybrid system for synergistically enhanced radiotherapy

2020 ◽  
Vol 8 (24) ◽  
pp. 5312-5319 ◽  
Author(s):  
Daoming Zhu ◽  
Meng Lyu ◽  
Wei Jiang ◽  
Meng Suo ◽  
Qinqin Huang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hybrid System ◽  
Therapeutic Regimen ◽  
Hypoxic Tumor

Although radiotherapy (RT) has been an effective therapeutic regimen for regulating most solid tumors, its effect is limited by the hypoxic tumor microenvironment and radio-tolerance of tumor cells to a large extent.

scholarly journals Anti-Tumor Responses By Ibrutinib and Anti-PD-1 Blockade Is Enhanced By Phosphatidylserine-Targeting Antibody Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5379-5379
Author(s):  
Jian Gong ◽  
Michael Gray ◽  
Jeff Hutchins ◽  
Bruce Freimark
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Combination Therapy ◽  
B Cell ◽  
Cell Line ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Triple Negative

Abstract Introduction: Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane that becomes exposed on vascular endothelial cells and tumor cells in the tumor microenvironment, particularly in response to chemotherapy and irradiation. Binding of antibodies targeting PS on the tumor endothelial cells and tumors induces the recruitment of immune cells and engages the immune system to destroy tumor and associated vasculature and by blocking the immunosuppressive action of PS. Recent studies have demonstrated that PS-targeting antibodies enhance the anti-tumor activity of immune checkpoint antibody blockade to CTLA-4 and PD-1 in mouse breast and melanoma tumor models (Freimark et al. Cancer Immunol. Res. 2016; Gray et al. Breast Cancer Res 2016). Ibrutinib is an approved anticancer drug targeting B-cell malignancies that is a selective, covalent inhibitor of the enzyme Bruton's tyrosine kinase(BTK) in B-cell tumors. Data from recent mouse tumor studies demonstrate that ibrutinib in combination with anti-PD-1 antibody blockade inhibits growth of solid tumors (lacking BTK expression) suggesting that ibrutinib may inhibit kinases of the immune system such as interleukin-2 inducible T-cell kinase (ITK), to enhance specific anti-tumor responses (Sagiv-Barfli et al. PNAS 20 2015). Methods: The present study was conducted to evaluate the anti-tumor effects of combination therapy including PS-targeting antibody mouse chimeric 1N11 (mch1N11), ibrutinib (32765) and anti-PD-1 antibody using C57BL/6 mice bearing triple negative E0771 breast tumors. Tumors were staged to an initial volume of ~100mm3and randomized to treatment groups (N=10) with mch1N11 or isotype at 10 mg/kg qw, anti-PD-1 at 2.5 mg/kg qw or ibrunitib 6 mg/kg or vehicle qd x 8. Tumor volumes were measured twice per week to determine tumor growth inhibition (TGI) relative to control treated animals until a maximum volume of 1500-2000mm3. The in vitro sensitivity of E0771 tumor cells to ibrutinib was compared to drug sensitive Jeko-1 lymphoma cells in a 72 hour growth and viability assay. Results: The E0771 cell line is resistant in vitroto 10 mM ibrutinib compared to the drug-sensitive Jeko-1 cell line (Figure 1). Mice bearing E0771 tumors treated with mch1N11, ibrutinib and anti-PD-1 alone had 22.2%, 23.5% and 32.6% TGI respectively. Combination of two agents increased the TGI for mch1N11 and ibrutinib to 30.5%, ibrutinib and anti-PD-1 to 34.5%, mch1N11 and anti-PD-1 to 36.1%. A triple combination therapy had statistically greater TGI compared to control treated mice (59.9%, p = 0.0084) and was greater than single and double combination therapies. Conclusion:Treatment of solid tumors with a combination of inhibitors that target PS, ITK and the PD-1/PD-L1 axis in the tumor microenvironment provides a novel treatment for solid tumors, including triple negative breast cancer. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Gong: Peregrine Pharmaceuticals, Inc.: Employment. Gray:Peregrine Pharmaceuticals, Inc.: Employment. Hutchins:Peregrine Pharmaceuticals, Inc.: Employment. Freimark:Peregrine Pharmaceuticals, Inc.: Employment.

scholarly journals Induced Pluripotent Stem Cell-derived CAR-Macrophage Cells with Antigen-dependent Anti-Cancer Cell Functions for Liquid and Solid Tumors

2020 ◽  
Author(s):  
Li Zhang ◽  
Lin Tian ◽  
Xiaoyang Dai ◽  
Hua Yu ◽  
Jiajia Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Solid Tumor ◽  
Cell Activity ◽  
Macrophage Cells ◽  
Anti Cancer ◽  
Induced Pluripotent

AbstractThe Chimera antigen receptor (CAR)-T cell therapy has gained great success in the clinic. However, there are still major challenges for its wider applications in a variety of cancer types including lack of effectiveness due to the highly complex tumor microenvironment, and the forbiddingly high cost due to personalized manufacturing procedures. In order to overcome these hurdles, numerous efforts have been spent focusing on optimizing Chimera Antigen Receptors, engineering and improving T cell capacity, exploiting features of subsets of T cell or NK cells, or making off-the-shelf universal T cells. Here, we developed induced pluripotent stem cells (iPSCs)-derived, CAR-expressing macrophage cells (CAR-iMac). These cells showed antigen-dependent macrophage functions such as expression and secretion of cytokines, polarization toward the pro-inflammatory/anti-tumor state, and phagocytosis of tumor cells, as well as some in vivo anti-cancer cell activity for both liquid and solid tumors. This technology platform for the first time provides an unlimited source of iPSC-derived engineered CAR-macrophage cells which could be utilized to eliminate cancer cells or modulate the tumor microenvironment in liquid and solid tumor immunotherapy.One sentence summaryWe developed CAR-expressing iPSC-induced macrophage cells that have antigen-dependent phagocytosis and pro-inflammatory functions and anti-cancer cell activity for both liquid and solid tumor cells.

scholarly journals The acidic tumor microenvironment: a target for smart cancer nano-theranostics

2017 ◽  
Vol 5 (2) ◽  
pp. 269-286 ◽  
Author(s):  
Liangzhu Feng ◽  
Ziliang Dong ◽  
Danlei Tao ◽  
Yicheng Zhang ◽  
Zhuang Liu
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Effective Treatment ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Future Perspectives ◽  
Ph Responsive ◽  
The Future ◽  
Precise Diagnosis ◽  
Glycolytic Rate

Abstract The acidic tumor microenvironment (TME), which mainly results from the high glycolytic rate of tumor cells, has been characterized as a hallmark of solid tumors and found to be a pivotal factor participating in tumor progression. Recently, due to the increasing understanding of the acidic TME, it has been shown that the acidic TME could be utilized as a multifaceted target during the design of various pH-responsive nanoscale theranostic platforms for the precise diagnosis and effective treatment of cancers. In this article, we will give a focused overview on the latest progress in utilizing this characteristic acidic TME as the target of nano-theranostics to enable cancer-specific imaging and therapy. The future perspectives in the development of acidic TME-targeting nanomedicine strategies will be discussed afterwards.

LOCAL HYPERTHERMIA IN TREATMENT FOR MALIGNANT BRAIN TUMORS

2018 ◽  
Vol 64 (1) ◽  
pp. 54-61
Author(s):  
A. Ryabova ◽  
O. Gribova ◽  
V. Novikov ◽  
E. Choinzonov ◽  
Zh. Starceva ◽  
...  
Keyword(s):  
Experimental Data ◽  
Radiation Therapy ◽  
Brain Tumors ◽  
Tumor Cells ◽  
Combined Treatment ◽  
Complex Treatment ◽  
Local Hyperthermia ◽  
Malignant Brain Tumors ◽  
Sensitizing Effect ◽  
Methods Of Treatment

Unsatisfactory results of complex treatment for malignant brain tumors stimulate search of new effective methods of treatment. Radiation therapy is an integral part of the combined treatment but often does not influence lethally on resistant tumor cells. Thereby in recent decades there has been an active search for different modifiers, which can increase the sensitivity of tumors to chemotherapy and radiotherapy. One of the universal sensitizers is the local hyperthermia. Experimental data showed that the effect of high temperatures had both a direct damaging effect on tumor cells and a sensitizing effect. The literature review given in the article provides an overview of the existing methods of the local hyperthermia for brain tumors treatment.

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

347 Clinical outcomes of ovarian cancer patients treated with ALKS 4230, a novel engineered cytokine, in combination with pembrolizumab: ARTISTRY-1 trial

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A372-A373
Author(s):  
Ira Winer ◽  
Lucy Gilbert ◽  
Ulka Vaishampayan ◽  
Seth Rosen ◽  
Christopher Hoimes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Marker ◽  
Solid Tumors ◽  
Cd8 T Cells ◽  
Comprehensive Cancer Center ◽  
List Type ◽  
Link Type ◽  
Heavily Pretreated

BackgroundALKS 4230 is a novel engineered cytokine that selectively targets the intermediate-affinity interleukin-2 receptor complex to activate CD8+ T cells and natural killer cells.1 The ARTISTRY-1 trial (NCT02799095) has shown encouraging efficacy and acceptable tolerability of ALKS 4230 among patients with advanced solid tumors.2 We report a detailed analysis of ovarian cancer (OC) patients who received combination therapy in ARTISTRY-1.MethodsARTISTRY-1 is an ongoing multicohort phase 1/2 trial exploring intravenous ALKS 4230 as monotherapy and combined with pembrolizumab. OC patients were enrolled into a cohort with mixed anti PD 1/L1 unapproved tumor types who had progressed on prior chemotherapy. OC patients received ALKS 4230 (3 µg/kg) on days 1–5 and pembrolizumab (200 mg) on day 1 of a 21 day cycle. Outcomes presented include antitumor activity (RECIST v1.1) and safety as of 7/24/2020. To evaluate changes in tumor microenvironment (TME), baseline and on-treatment biopsies were collected.ResultsFourteen heavily pretreated patients with OC were enrolled. Patients received a median of 5 (range, 2 11) prior regimens and all were previously treated with platinum based therapy. Among 13 evaluable patients with ≥1 assessment, 9 experienced disease control and 4 experienced disease progression; median treatment duration was approximately 7 weeks. Three patients experienced an objective response, including 1 complete response, 1 partial response (PR), and 1 unconfirmed PR; all were platinum resistant and negative for BRCA mutations. Five patients experienced tumor burden reductions (table 1). Treatment-related adverse events at the doses tested have generally been transient and manageable, with the majority being grade 1 and 2 in severity. Overall, based on preliminary data, the combination with ALKS 4230 did not demonstrate any additive toxicity to that already established with pembrolizumab alone. Additional safety and efficacy data are being collected in ongoing cohorts. In the monotherapy dose escalation portion of the study, ALKS 4230 alone increased markers of lymphocyte infiltration in 1 paired melanoma biopsy (1 of 1; on treatment at cycle 2); CD8+ T cell density and PD-L1 tumor proportion score increased 5.2- and 11 fold, respectively, supporting evidence that ALKS 4230 has immunostimulatory impact on the TME and providing rationale for combining ALKS 4230 with pembrolizumab (figure 1).Abstract 347 Table 1Summary of response observations among patients with ovarian cancerAbstract 347 Figure 1Increased markers of lymphocyte tumor infiltrationAn increase in CD3+CD8+ T cells (A, red = CD3; blue = CD8; purple = CD3+CD8+; teal = tumor marker), GranzymeB (B, red = CD8; green = granzymeB; yellow = granzymeB+CD8+; teal = tumor marker), and PD-L1 (C, red = PD-L1; blue = tumor marker) in the tumor microenvironment of a single patient was observed after the patient received monotherapy ALKS 4230ConclusionsThe combination of ALKS 4230, an investigational agent, and pembrolizumab demonstrates an acceptable safety profile and provides some evidence of tumor shrinkage and disease stabilization in some patients with heavily pretreated OC. This regimen could represent a new therapeutic option for these patients.AcknowledgementsThe authors would like to thank all of the patients who are participating in this trial and their families. The trial is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel and funded by Alkermes, Inc.Trial RegistrationClinicalTrials. gov NCT02799095Ethics ApprovalThis trial was approved by Ethics and Institutional Review Boards (IRBs) at all trial sites; IRB reference numbers 16–229 (Dana-Farber Cancer Institute), MOD00003422/PH285316 (Roswell Park Comprehensive Cancer Center), 20160175 (Western IRB), i15-01394_MOD23 (New York University School of Medicine), TRIAL20190090 (Cleveland Clinic), and 0000097 (ADVARRA).ReferencesLopes JE, Fisher JL, Flick HL, Wang C, Sun L, Ernstoff MS, et al. ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy. J Immunother Cancer 2020;8:e000673. doi: 10.1136/jitc-2020-000673.Vaishampayan UN, Muzaffar J, Velcheti V, Winer I, Hoimes CJ, Rosen SD, et al. ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumors (ARTISTRY-1). Oral presentation at: European Society for Medical Oncology Annual Meeting; September 2020; virtual.

scholarly journals Hypoxia and the Tumor Microenvironment

2021 ◽  
Vol 20 ◽  
pp. 153303382110363
Author(s):  
Yue Li ◽  
Long Zhao ◽  
Xiao-Feng Li
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Poor Prognosis ◽  
Tumor Biology ◽  
Metastatic Potential ◽  
Tumor Detection ◽  
Tumor Aggressiveness

Hypoxia is an important feature of the tumor microenvironment, and is closely associated with cell proliferation, angiogenesis, metabolism and the tumor immune response. All these factors can further promote tumor progression, increase tumor aggressiveness, enhance tumor metastatic potential and lead to poor prognosis. In this review, these effects of hypoxia on tumor biology will be discussed, along with their significance for tumor detection and treatment.

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