scholarly journals Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples

2020 ◽  
Author(s):  
Qiang Liu ◽  
Yihang Qi ◽  
Jie Zhai ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cell ◽  
Immune Checkpoints ◽  
Cell Populations ◽  
Potential Biomarker ◽  
The Impact

Abstract Background Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, a large number of cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, is a protein Coding gene served as alternative inhibitory receptors to be targeted in the clinic. The impact of LAG3 on immune cell populations and co-regulation of immune response in breast cancer remained largely unknown. Methods To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from a total of 2994 breast cancer patients. Results We observed that LAG3 was closely correlated with major molecular and clinical characteristics, and was more likely to be enriched in higher malignant subtype, suggesting LAG3 was a potential biomarker of triple-negative breast cancer. Furthermore, we estimated the landscape of relationship between LAG3 and ten types of cell populations in breast cancer. Gene ontology analysis revealed LAG3 were strongly correlated with immune response and inflammatory activities. We investigated the correlation pattern between LAG3 and immune modulators in pan-cancer, especially the synergistic role of LAG3 with other immune checkpoints members in breast cancer. Conclusions LAG3 expression was closely related to malignancy of breast cancer and might serve as a potential biomarker; LAG3 might plays an important role in regulating tumor immune microenvironment, not only T cells, but also other immune cells. More importantly, LAG3 might synergize with CTLA4, PD1/ PDL1 and other immune checkpoints, thereby lending more evidences to combination cancer immunotherapy by targeting LAG3, PD1/PDL1, and CTLA4 together.

scholarly journals Molecular and Clinical Characterization of LAG3 in Breast Cancer Through 2994 Samples

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Liu ◽  
Yihang Qi ◽  
Jie Zhai ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cell ◽  
Immune Checkpoints ◽  
Cell Populations ◽  
Breast Cancer Patients ◽  
Correlation Pattern ◽  
Potential Biomarker

Despite the promising impact of cancer immunotherapy targeting CTLA4 and PD1/PDL1, numerous cancer patients fail to respond. LAG3 (Lymphocyte Activating 3), also named CD233, serves as an alternative inhibitory receptor to be targeted in the clinic. The impacts of LAG3 on immune cell populations and coregulation of immune responses in breast cancer remain largely unknown. To characterize the role of LAG3 in breast cancer, we investigated transcriptome data and associated clinical information derived from 2,994 breast cancer patients. We estimated the landscape of the relationship between LAG3 and 10 types of cell populations of breast cancer. We investigated the correlation pattern between LAG3 and immune modulators in pancancer, particularly the synergistic role of LAG3 with other immune checkpoint members in breast cancer. LAG3 expression was closely related to the malignancy of breast cancer and may serve as a potential biomarker. LAG3 may play an important role in regulating the tumor immune microenvironment of T cells and other immune cells. More important, LAG3 may synergize with CTLA4, PD1/PDL1, and other immune checkpoints, thereby contributing more evidence to improve combination cancer immunotherapy by simultaneously targeting LAG3, PD1/PDL1, and CTLA4.

Effect of TCHL-based therapy on immune cell content in on-treatment, neoadjuvant-treated HER2-positive breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 583-583
Author(s):  
Niamh M. Keegan ◽  
Sinead Toomey ◽  
Joanna Fay ◽  
Stephen F. Madden ◽  
Bruce Moran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Cell Populations ◽  
Breast Cancer Patients ◽  
Myeloid Dendritic Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
The Impact ◽  
Positive Breast Cancer

583 Background: In the TCHL trial (NCT01485926) 78 women with HER2-positive breast cancer (BC) underwent neo-adjuvant treatment with either TCH (Docetaxel, Carboplatin, Trastuzumab) or TCHL (TCH + Lapatinib) therapy. Of the 78 patients, 24 consented to an optional on-treatment biopsy 20 days after 1 cycle of therapy. We analysed the impact of tumour infiltrating lymphocytes (TILs) on pathological complete response (pCR) and also determined the impact of TCH/TCHL therapy on immune cell modulation after 20 days of treatment. Methods: We assessed TIL and stromal lymphocytes (SL) counts using immunohistochemical staining with Haemotoxalyin+Eosin, AE1/AE3 and CD45 in formalin fixed paraffin embedded (FFPE) baseline biopsy samples and in fresh frozen (FF) biopsies taken 20-days post cycle 1 (Day-20) of TCH/TCHL. RNA libraries were generated, using the Truseq mRNA library prep kit on the Neoprep platform and sequenced on the NextSeq 500. We measured the transcriptomic profile of 8 pre and on-treatment sample pairs and then used the Microenvironment Cell Populations (MCP)-counter method to measure the abundance of 10 immune cell populations (T cells, CD8 T cells, cytotoxic lymphocytes, NK cells, B lineage, myeloid dendritic cells, neutrophils, endothelial cells and fibroblasts). Results: We found that higher baseline levels of TILs (p = 0.045) but not SL were associated with an increased likelihood of a patient achieving a pCR to TCH/L based therapy. We found in day 20 on-treatment biopsies of women that subsequently went onto have a pCR that levels of SLs but not TILs were significantly higher (p = 0.049) than in those women who did not have a pCR. Finally we found significant increases in the level of monocytes (p = 0.05) and fibroblasts (p = 0.01), but not other immune cell populations, in the day 20 on-treatment biopsies in comparison with the mutated pre-treatment biopsies. Conclusions: In our study baseline TILs but not SLs have a predictive role in the likelihood of a patient achieving a pCR. We also found that TCHL based therapy significantly altered both monocytes and fibroblasts, indicating a possible role for these immune subtypes in response to TCHL therapy.

Association of phosphatidylinositol 3-kinase (PI3K) pathway activation with increased immune checkpoint expression in colorectal cancer (CRC) patients.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 653-653 ◽  
Author(s):  
Maliha Nusrat ◽  
Jason Roszik ◽  
Riham Katkhuda ◽  
David Menter ◽  
Kanwal Pratap Singh Raghav ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Protein Expression ◽  
Immune Cell ◽  
Early Stage ◽  
Pi3k Pathway ◽  
Genetic Alterations ◽  
Immune Checkpoints ◽  
Pik3ca Mutations ◽  
The Impact

653 Background: PI3K pathway is a known modulator of anti-tumor immune response and is frequently activated in CRC through genetic alterations such as PTEN loss (PTENloss) and PIK3CA mutations (PIK3CAmut). This study aims to determine the impact of these alterations on immune cell infiltration, priming and activation in early stage CRC patients (pts). Methods: Immune infiltrates and checkpoints were evaluated using quantitative immunohistochemistry (IHC) on primary CRC (N = 59) for both center of tumor (CT) and invasive margin (IM). Pts were evaluated by presence or absence of either PTENloss or PIK3CAmut (collectively termed PI3K pathway alterations). Microsatellite unstable (MSI) and stable (MSS) tumors were analyzed separately. Clinicopathologic data was examined for potential associations with PI3K pathway alterations. Separately, mRNA data (Agilent) was obtained for immune related genes from an internal cohort with PTEN and PIK3CA annotation (N = 73). Results: 59 pts comprised IHC cohort (40 MSS, 19 MSI); 23 pts (39%) had PTENloss or PIK3CAmut. In Agilent cohort, 16 of 73 pts (22%) had PI3K pathway alterations. In MSS CRC, these alterations were more common in CMS1 (p = 0.03), on right side (p = 0.048) and with peritumoral lymphocytes (p = 0.031). MSS pts with PI3K pathway alterations had higher PD1 protein expression (p = 0.04), 2.1 and 2.3 times increased density of CD3+ (p = 0.01) and CD8+ (p = 0.04) cells respectively, and higher Granzyme B protein expression (p = 0.04) in the CT. These pts also had higher PDL1 gene expression (p = 0.046). MSS CRC pts with PIK3CAmut similarly had 2 times more PDL1 protein expression in epithelial cells of the IM (p = 0.01). Alternate checkpoints were also increased in pts with PI3K pathway alterations, including higher protein expression of LAG3 in CT (P = 0.046) and higher gene expression of CTLA4, TIM3, and TIGIT (P < 0.05 for all). Conclusions: PI3K pathway activated MSS CRC is associated with increased immune engagement, but also upregulation of key immune checkpoints in early stage tumors resulting in an ineffective immune response. Combination of PI3K pathway inhibition with immunotherapy merits investigation in this subset of pts.

scholarly journals The immune response and aging in chronic inflammatory demyelinating polyradiculoneuropathy

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Kathleen M. Hagen ◽  
Shalina S. Ousman
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Older Patients ◽  
Potential Role ◽  
Immune Cell ◽  
Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽  
Cell Populations ◽  
Relapsing Remitting ◽  
Progressive Course

AbstractChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consists of various autoimmune subtypes in which the peripheral nervous system (PNS) is attacked. CIDP can follow a relapsing-remitting or progressive course where the resultant demyelination caused by immune cells (e.g., T cells, macrophages) and antibodies can lead to disability in patients. Importantly, the age of CIDP patients has a role in their symptomology and specific variants have been associated with differing ages of onset. Furthermore, older patients have a decreased frequency of functional recovery after CIDP insult. This may be related to perturbations in immune cell populations that could exacerbate the disease with increasing age. In the present review, the immune profile of typical CIDP will be discussed followed by inferences into the potential role of relevant aging immune cell populations. Atypical variants will also be briefly reviewed followed by an examination of the available studies on the immunology underlying them.

Abstract PS17-37: Immune cell populations in peripheral blood of metastatic breast cancer patients under CDK4/6 inhibitors

2021 ◽  
Author(s):  
Soraia Lobo-Martins ◽  
Patrícia Corredeira ◽  
Patrícia Borges Alves ◽  
Marília Antunes ◽  
Ângela Rodrigues ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Cell Populations ◽  
Breast Cancer Patients

scholarly journals Effect of Propofol and Desflurane on Immune Cell Populations in Breast Cancer Patients: A Randomized Trial

2015 ◽  
Vol 30 (10) ◽  
pp. 1503 ◽  
Author(s):  
Jae Hee Woo ◽  
Hee Jung Baik ◽  
Chi Hyo Kim ◽  
Rack Kyung Chung ◽  
Dong Yeon Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trial ◽  
Cancer Patients ◽  
Immune Cell ◽  
Cell Populations ◽  
Breast Cancer Patients

scholarly journals TIGIT-related transcriptome profile and its association with tumor immune microenvironment in breast cancer

2021 ◽  
Vol 41 (3) ◽  
Author(s):  
Qin Zhang ◽  
Chaowei Gao ◽  
Jianqiang Shao ◽  
Zunyi Wang
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Large Scale ◽  
Immune Cell ◽  
Molecular Taxonomy ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Breast Cancer Patients ◽  
Transcriptome Profile

Abstract Immune checkpoints are intensively investigated as targets in cancer immunotherapy. T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) are recently emerging as a novel promising target in cancer immunotherapy. Herein, we systematically investigated TIGIT-related transcriptome profile and relevant clinical information derived from a total of 2994 breast cancer patients recorded in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). We uncovered the relationship between TIGIT and major molecular and clinical characteristics in breast cancer. More importantly, we depicted the landscape of associations between TIGIT and other immune cell populations. Gene ontology analyses and Gene Set Variation Analysis (GSVA) of genes correlated with TIGIT revealed that TIGIT were mainly involved in immune responses and inflammatory activities. In summary, TIGIT expression was tightly related to the aggressiveness of breast cancer; TIGIT might manipulate anti-tumor immune responses by impacting not only T cells but also other immune cells. To the best of our knowledge, this is by far the most comprehensive and largest study characterizing the molecular and clinical features of TIGIT in breast cancer through large-scale transcriptome data.

scholarly journals Comprehensive Analysis of Innate Immunophenotyping Based on Immune Score Predicting Immune Alterations and Prognosis in Breast Cancer Patients

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Weiguang Liu ◽  
Lingling Xia ◽  
Zhengmiao Xia ◽  
Liming Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Risk Model ◽  
Innate Immune ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients ◽  
Score Model

Breast cancer is the most common cancer, with the highest mortality rate and the most diagnosed cancer type in women worldwide. To identify the effect innate immune checkpoint for breast cancer immunotherapy, the innate immune prognostic biomarkers were selected through the ICI score model and the risk model in breast cancer patients. Moreover, the reliability and accuracy of the ICI score model and the risk model were further examined through the analysis of breast cancer prognosis and immune cell infiltration. The pan cancer analysis further confirmed and selected CXCL9 as the key innate immune checkpoint for breast cancer immunotherapy and identified three small molecular drugs for target CXCL9 through molecular docking analysis. In summary, CXCL9 significantly correlated with the prognostic of breast cancer and immune cell infiltration and could be innate immune checkpoint for breast cancer immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document