What Happens to the Immune Microenvironment After PD-1 Inhibitor Therapy?

The fruitful results of tumor immunotherapy establish its indispensable status in the regulation of the tumorous immune context. It seems that the treatment of programmed cell death receptor 1 (PD-1) blockade is one of the most promising approaches for cancer control. The significant efficacy of PD-1 inhibitor therapy has been made in several cancer types, such as breast cancer, lung cancer, and multiple myeloma. Even so, the mechanisms of how anti-PD-1 therapy takes effect by impacting the immune microenvironment and how partial patients acquire the resistance to PD-1 blockade have yet to be studied. In this review, we discuss the cross talk between immune cells and how they promote PD-1 blockade efficacy. In addition, we also depict factors that may underlie tumor resistance to PD-1 blockade and feasible solutions in combination with it.

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Immunotherapy for Soft Tissue Sarcoma: Tomorrow Is Only a Day Away

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_157439 ◽

2016 ◽

pp. 281-290 ◽

Cited By ~ 2

Author(s):

Alex Lee ◽

Paul Huang ◽

Ronald P. DeMatteo ◽

Seth M. Pollack

Keyword(s):

T Cells ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Immune Responses ◽

Cytotoxic Lymphocytes ◽

Immune Microenvironment ◽

Advanced Soft Tissue Sarcoma ◽

Novel Treatments ◽

Cancer Types ◽

Made In

Despite the advances taking place for patients with many types of cancer, to date there has been little success in meeting the great need for novel treatments of advanced soft tissue sarcoma with effective immunologic therapies. Here, we review recent clinical and preclinical data that indicate immune responses against sarcomas occur spontaneously and can also be successfully provoked. Efforts to manipulate the sarcoma immune microenvironment have the potential to eradicate disease and may also sensitize tumors to other tumor-targeted immunotherapeutic approaches. Other approaches, including vaccines and genetic engineering of T cells, offer a promising opportunity to actively direct cytotoxic lymphocytes toward antigen-bearing sarcomas. Drawing parallels with recent advances made in other cancer types, we identify ways in which sarcomas can be included in the ongoing immunotherapy revolution.

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HGF/MET and the Immune System: Relevance for Cancer Immunotherapy

International Journal of Molecular Sciences ◽

10.3390/ijms19113595 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3595 ◽

Cited By ~ 22

Author(s):

Federica Papaccio ◽

Carminia Della Corte ◽

Giuseppe Viscardi ◽

Raimondo Di Liello ◽

Giovanna Esposito ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Immunotherapy ◽

Acquired Resistance ◽

Death Receptor ◽

Death Receptor Ligand ◽

Cancer Types ◽

Mesenchymal Epithelial Transition Factor ◽

Hepatocyte Growth ◽

Cell Death Receptor

An overactivation of hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) axis promotes tumorigenesis and tumor progression in various cancer types. Research data recently evidenced that HGF/MET signaling is also involved also in the immune response, mainly modulating dendritic cells functions. In general, the pathway seems to play an immunosuppressive role, thus hypothesizing that it could constitute a mechanism of primary and acquired resistance to cancer immunotherapy. Recently, some approaches are being developed, including drug design and cell therapy to combine MET and programmed cell death receptor-1 (PD-1)/programmed cell death receptor-ligand 1 (PD-L1) inhibition. This approach could represent a new weapon in cancer therapy in the future.

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Killing Prostate Cancer Cells and Endothelial Cells with a VEGF-Triggered Cell Death Receptor

10.21236/ada476353 ◽

2005 ◽

Author(s):

Timothy P. Quinn

Keyword(s):

Prostate Cancer ◽

Endothelial Cells ◽

Cell Death ◽

Cancer Cells ◽

Death Receptor ◽

Prostate Cancer Cells ◽

Cell Death Receptor

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Immunotherapy in Glioblastoma: A Clinical Perspective

Cancers ◽

10.3390/cancers13153721 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3721

Author(s):

Nicolas Desbaillets ◽

Andreas Felix Hottinger

Keyword(s):

Cancer Vaccines ◽

Adoptive Cell Transfer ◽

Oncolytic Viruses ◽

Clinical Perspective ◽

Immune Microenvironment ◽

Medical Need ◽

Great Hope ◽

Car T ◽

Cancer Types ◽

Proof Of Efficacy

Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. In this review, the rationale underlying immune targeting of glioblastoma, as well as the challenges faced when targeting these highly immunosuppressive tumors, are discussed. Innovative immune-targeting strategies including cancer vaccines, oncolytic viruses, checkpoint blockade inhibitors, adoptive cell transfer, and CAR T cells that have been investigated in glioblastoma are reviewed. From a clinical perspective, key clinical trial findings and ongoing trials are discussed for each approach. Finally, limitations, either biological or arising from trial designs are analyzed, and strategies to overcome them are presented. Proof of efficacy for immunotherapy approaches remains to be demonstrated in glioblastoma, but our rapidly expanding understanding of its biology, its immune microenvironment, and the emergence of novel promising combinatorial approaches might allow researchers to finally fulfill the medical need for GBM patients.

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Curcumin Induces Small Cell Lung Cancer NCI-H446 Cell Apoptosis via the Reactive Oxygen Species-Mediated Mitochondrial Pathway and Not the Cell Death Receptor Pathway

DNA and Cell Biology ◽

10.1089/dna.2011.1300 ◽

2012 ◽

Vol 31 (2) ◽

pp. 139-150 ◽

Cited By ~ 53

Author(s):

Cheng-Liang Yang ◽

Ye-Gang Ma ◽

Yi-Xue Xue ◽

Yong-Yu Liu ◽

Hui Xie ◽

...

Keyword(s):

Lung Cancer ◽

Reactive Oxygen Species ◽

Cell Death ◽

Cell Apoptosis ◽

Death Receptor ◽

Mitochondrial Pathway ◽

Small Cell ◽

Oxygen Species ◽

Small Cell Lung ◽

Cell Death Receptor

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Programmed Cell Death Receptor Ligand 1 Modulates the Regulatory T Cells’ Capacity to Repress Shock/Sepsis–Induced Indirect Acute Lung Injury by Recruiting Phosphatase Src Homology Region 2 Domain-Containing Phosphatase 1

Shock ◽

10.1097/shk.0000000000000247 ◽

2015 ◽

Vol 43 (1) ◽

pp. 47-54 ◽

Cited By ~ 16

Author(s):

Lunxian Tang ◽

Jianwen Bai ◽

Chun-Shiang Chung ◽

Joanne Lomas-Neira ◽

Yaping Chen ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

Acute Lung Injury ◽

Programmed Cell Death ◽

Lung Injury ◽

Death Receptor ◽

Receptor Ligand ◽

Death Receptor Ligand ◽

Src Homology ◽

Cell Death Receptor

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IMMUNOLOGICAL DISORDERS OF THE REPRODUCTIVE SYSTEM THAT OCCUR WHEN EXPOSED TO BENZENE, IN EMPLOYEES OF OIL-PRODUCING ENTERPRISES

10.31089/978-5-6042929-2-1-2021-1-313-316 ◽

2021 ◽

Author(s):

I.V. Leshkova ◽

◽

O.V. Dolgih ◽

O.YU. Ustinova

Keyword(s):

Cell Death ◽

Reproductive Health ◽

Reproductive System ◽

Death Receptor ◽

Annexin V ◽

Reference Level ◽

Immunological Disorders ◽

Cellular Expression ◽

Cell Death Receptor

Abstract. Introduction. The protection of the reproductive health of the working-age population is the most important direction of State policy. In 5-15% of cases, the causes of reproductive dysfunction are immunological disorders. Benzene belongs to the group of industrial reprotoxicants, however, its effect of benzene on the reproductive system has not been sufficiently studied. Objective: to study the immunological aspects of the effect of benzene on the reproductive system. Methods. We examined 50 men exposed to benzene with reproductive disorders (26-49 years old), as well as 4 workers with normal sexual function aged 53-60 years. Spontaneous and induced changes in the cellular expression of apoptosis markers were studied. For the study, the ANNEXIN V-FITC/7-AAD kit was used for the detection of cells that have undergone apoptosis. The experiment was conducted in vitro using a biological medium (ejaculate). A factor of the chemical nature was benzene. Results. According to the results of the comparative analysis, there were no significant deviations of pathogenetic tests of immunological markers in comparison with the reference level in the spontaneous expression samples, but there was an excess of expression of the CD95 + cell death receptor (p<0.05) in 30% of the samples examined, and a decrease in the number of Annexin V-FITC+7AAD negative cells (without reaching the significance level) in samples with a load of (15%). There was a difference in the expression levels of CD95+ and CD25+ CD-reception indicators by 20% and 10% in relation to the spontaneous level (p<0.05). Representatives of the chemical group of aromatic hydrocarbons realize reprotoxicity, using the mechanism of excessive induction of the membrane signaling of the cell death receptor, accelerate the natural program of cell death by approximately 20% compared to the state of reproductive cells that were not stimulated. Conclusion. At the present stage, one of the tasks of occupational medicine is to study the effect of chemicals on the processes of reproduction, to develop new approaches to assessing the risk of their impact on the reproductive health of workers.

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The Hypoxic Microenvironment of Breast Cancer Cells Promotes Resistance in Radiation Therapy

Frontiers in Oncology ◽

10.3389/fonc.2020.629422 ◽

2021 ◽

Vol 10 ◽

Author(s):

Cordell Gilreath ◽

Marjan Boerma ◽

Zhiqiang Qin ◽

M. Keith Hudson ◽

Shanzhi Wang

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Ionizing Radiation ◽

Tumor Hypoxia ◽

Cancer Control ◽

Tumor Resistance ◽

Cancer Proliferation ◽

Cancer Society ◽

Recent Developments ◽

Proliferation And Metastasis

The American Cancer Society has estimated an expected 279,100 new breast cancer cases, and an expected 42,690 breast cancer deaths in the U.S. for the year 2020. This includes an estimated 276,480 women who are expected to be diagnosed. Radiation therapy, also called ionizing radiation therapy, is one of the most frequently used methods in the treatment of breast cancer. While radiation therapy is used in the treatment of more than 50% of all cancer cases, tumor resistance to ionizing radiation presents a major challenge for effective cancer treatment. Most tumor cells are in a hypoxic microenvironment that promotes resistance to radiation therapy. In addition to radiation resistance, the hypoxic microenvironment also promotes cancer proliferation and metastasis. In this review, we will discuss the hypoxic microenvironment of breast cancer tumors, related signaling pathways, breast cancer stem-like cells, and the resistance to radiation therapy. Recent developments in our understanding of tumor hypoxia and hypoxic pathways may assist us in developing new strategies to increase cancer control in radiation therapy.

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