scholarly journals PD-1 and PD-L1 correlated gene expression profiles and their association with clinical outcomes of breast cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cui Jiang ◽  
SunRun Cao ◽  
Na Li ◽  
Lei Jiang ◽  
Tao Sun
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Biological Process ◽  
Tolerance Induction ◽  
Lymphocyte Activation ◽  
Immune Checkpoints ◽  
Immune Infiltration ◽  
Process Tolerance

Abstract Background Immunotherapies that targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1) have obtained prominent success in breast cancer (BC). However, not all the patients benefit from the antibody therapy. This study aimed to identify PD-1/PD-L1 correlated genes and pathways as well as investigate their potential as prognostic marker in BC. Materials and methods By analysing transcriptional data of BC from TCGA, we identified PD-1 and PD-L1 correlated genes by WGCNA analysis and explored the biological process as well as pathways they enriched. Co-expression analysis were performed for PD-1/PD-L1 with immune infiltration and checkpoints. The prognostic value of PD-1 and PD-L1 were also investigated. Results PD-1 and PD-L1 expression showed significant difference in different molecular subtypes and stages. PD-1 correlated genes enriched in T cell activation, lymphocyte activation, leukocyte migration while PD-L1 correlated genes demonstrated enrichment including T cell apoptotic process, tolerance induction and cytolysis. Immune infiltration analysis suggested that PD-1 and PD-L1 were related with Neutrophils (r = 0.65, r = 0.48) and Fibroblasts (r = 0.59, r = 0.47). For immune checkpoints analysis, PD-1 was associated with HLA-A (r = 0.804) and INPP5D (r = 0.782) while PD-L1 correlated with CTLA4 (r = 0.843) and CD27 (r = 0.823). PD-1 was associated favorable survival of BC (HR = 0.67, P = 0.012) while PD-L1 did not demonstrate significant association with BC prognosis (HR = 0.85, P = 0.313). Conclusion PD-1 and PD-L1 correlated genes participated in biological process including T cell activation, lymphocyte activation, leukocyte migration, T cell apoptotic process, tolerance induction and cytolysis. PD-1/PD-L1 expression also demonstrated relation with immune infiltration and immune checkpoints. High PD-1 expression predicted better survival of breast cancer patients.

scholarly journals Immune Checkpoints, Inhibitors and Radionuclides in Prostate Cancer: Promising Combinatorial Therapy Approach

2021 ◽  
Vol 22 (8) ◽  
pp. 4109
Author(s):  
Mankgopo M. Kgatle ◽  
Tebatso M. G. Boshomane ◽  
Ismaheel O. Lawal ◽  
Kgomotso M. G. Mokoala ◽  
Neo P. Mokgoro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Cancer Control ◽  
Lymphocyte Activation ◽  
Immune Checkpoints ◽  
Mortality And Morbidity ◽  
Domain 3

Emerging research demonstrates that co-inhibitory immune checkpoints (ICs) remain the most promising immunotherapy targets in various malignancies. Nonetheless, ICIs have offered insignificant clinical benefits in the treatment of advanced prostate cancer (PCa) especially when they are used as monotherapies. Current existing PCa treatment initially offers an improved clinical outcome and overall survival (OS), however, after a while the treatment becomes resistant leading to aggressive and uncontrolled disease associated with increased mortality and morbidity. Concurrent combination of the ICIs with radionuclides therapy that has rapidly emerged as safe and effective targeted approach for treating PCa patients may shift the paradigm of PCa treatment. Here, we provide an overview of the contextual contribution of old and new emerging inhibitory ICs in PCa, preclinical and clinical studies supporting the use of these ICs in treating PCa patients. Furthermore, we will also describe the potential of using a combinatory approach of ICIs and radionuclides therapy in treating PCa patients to enhance efficacy, durable cancer control and OS. The inhibitory ICs considered in this review are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1), V-domain immunoglobulin suppressor of T cell activation (VISTA), indoleamine 2,3-dioxygenase (IDO), T cell Immunoglobulin Domain and Mucin Domain 3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), B7 homolog 3 (B7-H3) and B7-H4.

scholarly journals The association between CD28 gene rs3116496 polymorphism and breast cancer risk in Chinese women

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Yuxiang Yan ◽  
Xianbo Zhang
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mrna Level ◽  
Costimulatory Molecule ◽  
Lymphocyte Activation ◽  
Chinese Han ◽  
Bioinformatics Analyses ◽  
Increased Risk

T-lymphocyte activation plays an important role in suppressing the development of human cancers including breast cancer (BC). Cluster of differentiation 28 (CD28) is the primary T-cell costimulatory molecule and enhances T-cell activation and proliferation. To examine the role of CD28 gene polymorphism in BC, we conducted a case–control study involving 312 BC patients and 312 controls in a Chinese Han population. Bioinformatics analyses were conducted to analyze the expression level of CD28 and its association with overall survival (OS) of BC. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism (SNP) Scan™ Kit. Our results indicated that CD28 mRNA level was down-regulated in the BC patients, whereas high expression of CD28 showed better OS for BC. In addition, an increased risk of BC was associated with the rs3116496 CC genotype of CD28 gene (CC vs. TT). The significant association was also observed in the recessive model. In conclusion, CD28 may be a tumor suppressor gene and rs3116496 polymorphism of CD28 gene showed positively correlation with the increased risk of BC. However, larger studies with more diverse ethnic populations are needed to confirm these results.

scholarly journals Role of Ly-6 in lymphocyte activation. II. Induction of T cell activation by monoclonal anti-Ly-6 antibodies.

1986 ◽  
Vol 164 (3) ◽  
pp. 709-722 ◽  
Author(s):  
T R Malek ◽  
G Ortega ◽  
C Chan ◽  
R A Kroczek ◽  
E M Shevach
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Proliferative Response ◽  
Cell Activation ◽  
Critical Role ◽  
Lymphocyte Activation ◽  
Accessory Cells ◽  
Peripheral T Cells ◽  
Activation Cascade

The Ly-6 locus controls the expression and/or encodes for alloantigenic specificities found primarily on subpopulations of murine T and B lymphocytes. We have recently identified and characterized a new rat mAb, D7, that recognizes a nonpolymorphic Ly-6 specificity. After crosslinking by anti-Ig reagents or by Fc receptor-bearing accessory cells, mAb D7 could induce IL-2 production from T cell hybridomas, and in the presence of PMA could trigger a vigorous proliferative response in resting peripheral T cells. The addition of mAb D7 to cultures of antigen- and alloantigen-, but not mitogen-stimulated T cells resulted in a marked augmentation of the proliferative response. A number of other well-characterized mAbs to Ly-6 locus products could also stimulate a T cell proliferative response after crosslinking by anti-Ig and in the presence of PMA. These results strongly suggest that Ly-6 molecules may play a critical role in the T cell activation cascade, either as receptors for an unidentified soluble or cell-associated ligand or as transducing molecules that modulate signals initiated by antigen stimulation of the T3-Ti complex.

scholarly journals Checkpoint Inhibitors in Breast Cancer - Current Status and Future Directions

Breast Care ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Joachim Bischoff
Keyword(s):  
Breast Cancer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Death Receptor ◽  
Target Population ◽  
Current Status ◽  
Immune Checkpoints ◽  
Breast Cancer Patients

Antineoplastic agents directly targeting tumor cells have represented the major strategy of systemic anticancer therapy for many years. Nevertheless, overcoming resistance mechanisms remains a great challenge because treatment options are limited in many cases. From this point of view, immunotherapeutic approaches seem promising in a broad spectrum of solid tumors. These include in particular the currently available inhibitors directed against immune checkpoints leading to a significant T-cell activation. To date, the programmed death receptor 1 (PD-1) and its ligand are the most prominent targets in this context. However, the role of checkpoint inhibitors in the treatment of breast cancer is still being debated, and the main focus is on triple-negative breast cancer patients as a target population in many ongoing trials. Moreover, the potential superiority of combinations with other anticancer drugs such as cytotoxics and targeted agents will be discussed.

scholarly journals Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications

Science ◽  
2020 ◽  
Vol 369 (6508) ◽  
pp. eabc8511 ◽  
Author(s):  
Divij Mathew ◽  
Josephine R. Giles ◽  
Amy E. Baxter ◽  
Derek A. Oldridge ◽  
Allison R. Greenplate ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Integrated Analysis ◽  
Therapeutic Implications ◽  
Global Pandemic ◽  
Acute Viral Infection ◽  
Activation Characteristic ◽  
B Cell Subsets

Coronavirus disease 2019 (COVID-19) is currently a global pandemic, but human immune responses to the virus remain poorly understood. We used high-dimensional cytometry to analyze 125 COVID-19 patients and compare them with recovered and healthy individuals. Integrated analysis of ~200 immune and ~50 clinical features revealed activation of T cell and B cell subsets in a proportion of patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses reaching >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable with that in uninfected individuals. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. Our analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for the design of therapeutics and vaccines for COVID-19.

scholarly journals Interplay of tRNA-Derived Fragments and T Cell Activation in Breast Cancer Patient Survival

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2230 ◽  
Author(s):  
Nayang Shan ◽  
Ningshan Li ◽  
Qile Dai ◽  
Lin Hou ◽  
Xiting Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
T Cell ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cox Regression ◽  
Patient Survival ◽  
Significant Difference

Effector CD8+ T cell activation and its cytotoxic function are positively correlated with improved survival in breast cancer. tRNA-derived fragments (tRFs) have recently been found to be involved in gene regulation in cancer progression. However, it is unclear how interactions between expression of tRFs and T cell activation affect breast cancer patient survival. We used Kaplan–Meier survival and multivariate Cox regression models to evaluate the effect of interactions between expression of tRFs and T cell activation on survival in 1081 breast cancer patients. Spearman correlation analysis and weighted gene co-expression network analysis were conducted to identify genes and pathways that were associated with tRFs. tRFdb-5024a, 5P_tRNA-Leu-CAA-4-1, and ts-49 were positively associated with overall survival, while ts-34 and ts-58 were negatively associated with overall survival. Significant interactions were detected between T cell activation and ts-34 and ts-49. In the T cell exhaustion group, patients with a low level of ts-34 or a high level of ts-49 showed improved survival. In contrast, there was no significant difference in the activation group. Breast cancer related pathways were identified for the five tRFs. In conclusion, the identified five tRFs associated with overall survival may serve as therapeutic targets and improve immunotherapy in breast cancer.

Focused ultrasound therapy combined with pembrolizumab in metastatic breast cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS19-TPS19
Author(s):  
Patrick Michael Dillon ◽  
Bethany J Horton ◽  
Timothy Bullock ◽  
Christiana Brenin ◽  
David R. Brenin
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Focused Ultrasound ◽  
Metastatic Breast ◽  
High Energy ◽  
Antitumor Effects ◽  
Ablative Therapy ◽  
Metastatic Setting

TPS19 Background: Focused ultrasound (FUS) is an ablative therapy which can heat tumors rapidly to cell damaging temperatures and simultaneously perturb the microenvironment, the microvasculature, and the lymphatics. At typical energy levels, FUS can induce controlled apoptotic cell death rather than liquefactive necrosis. FUS does not involve radiation. FUS is a partially ablative therapy using high energy ultrasound waves to induce heat shock proteins, cytokine release and cellular mediated mechanisms resulting in T cell activation and recognition of tumor antigens. FUS has been demonstrated to be an effective method for inducing tumor antigen exposure and presentation to dendritic cells, thus acting as an auto-vaccine. Pembrolizumab (PBZ) is a PD-1 targeted antibody used in multiple solid tumors to augment T cell activation. It is hypothesized that the combination of these two modalities will result in T cell infiltration into breast tumors as well as systemic immune responses. Methods: In this pilot study, we will examine PBZ therapy in combination with FUS to assess for immune stimulation and antitumor effects at local ablation sites, distant non-treated sites and in the blood. Biopsy before and after treatments will examine the tissue in the peripheral zone of ablation as well as at distant metastatic sites for CD8 and CD4 T cells, MDSC’s, T-regulatory cells and cytokine responses. Twelve patients will be randomized to receive either PBZ 14 days before or 7 days after a single time FUS partial tumor ablation on day 15. Biopsies will be on days 1, 22 and 64 and tumor imaging will be every 12 weeks. Patients must have metastatic or unresectable breast cancer, adequate organ function, and prior therapy in the metastatic setting. They must also have a tumor in the breast or axilla amenable to FUS and biopsy. Clinical trial information: NCT03237572.

scholarly journals VISTA: A Target to Manage the Innate Cytokine Storm

2021 ◽  
Vol 11 ◽  
Author(s):  
Mohamed A. ElTanbouly ◽  
Yanding Zhao ◽  
Evelien Schaafsma ◽  
Christopher M. Burns ◽  
Rodwell Mabaera ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Constitutive Expression ◽  
Immune Checkpoints ◽  
Complete Suppression ◽  
Wide Range ◽  
The Impact

In recent years, the success of immunotherapy targeting immunoregulatory receptors (immune checkpoints) in cancer have generated enthusiastic support to target these receptors in a wide range of other immune related diseases. While the overwhelming focus has been on blockade of these inhibitory pathways to augment immunity, agonistic triggering via these receptors offers the promise of dampening pathogenic inflammatory responses. V-domain Ig suppressor of T cell activation (VISTA) has emerged as an immunoregulatory receptor with constitutive expression on both the T cell and myeloid compartments, and whose agonistic targeting has proven a unique avenue relative to other checkpoint pathways to suppress pathologies mediated by the innate arm of the immune system. VISTA agonistic targeting profoundly changes the phenotype of human monocytes towards an anti-inflammatory cell state, as highlighted by striking suppression of the canonical markers CD14 and Fcγr3a (CD16), and the almost complete suppression of both the interferon I (IFN-I) and antigen presentation pathways. The insights from these very recent studies highlight the impact of VISTA agonistic targeting of myeloid cells, and its potential therapeutic implications in the settings of hyperinflammatory responses such as cytokine storms, driven by dysregulated immune responses to viral infections (with a focus on COVID-19) and autoimmune diseases. Collectively, these findings suggest that the VISTA pathway plays a conserved, non-redundant role in myeloid cell function.

scholarly journals Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions

2020 ◽  
Author(s):  
Divij Mathew ◽  
Josephine R. Giles ◽  
Amy E. Baxter ◽  
Allison R. Greenplate ◽  
Jennifer E. Wu ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Therapeutic Interventions ◽  
Integrated Analysis ◽  
Global Pandemic ◽  
Acute Viral Infection ◽  
Activation Characteristic ◽  
B Cell Subsets

AbstractCOVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ∼200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three “immunotypes” associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines.

Sign in / Sign up

Export Citation Format

Share Document