scholarly journals Programmed Death-Ligand 1 (PD-L1) as Immunotherapy Biomarker in Breast Cancer

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 307
Author(s):  
Martín Núñez Abad ◽  
Silvia Calabuig-Fariñas ◽  
Miriam Lobo de Mena ◽  
Susana Torres-Martínez ◽  
Clara García González ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Malignant Neoplasm ◽  
Predictive Biomarker ◽  
Immune Checkpoints ◽  
Hormone Receptor Positive

Breast cancer constitutes the most common malignant neoplasm in women around the world. Approximately 12% of patients are diagnosed with metastatic stage, and between 5 and 30% of early or locally advanced BC patients will relapse, making it an incurable disease. PD-L1 ligation is an immune inhibitory molecule of the activation of T cells, playing a relevant role in numerous types of malignant tumors, including BC. The objective of the present review is to analyze the role of PD-L1 as a biomarker in the different BC subtypes, adding clinical trials with immune checkpoint inhibitors and their applicable results. Diverse trials using immunotherapy with anti-PD-1/PD-L1 in BC, as well as prospective or retrospective cohort studies about PD-L1 in BC, were included. Despite divergent results in the reviewed studies, PD-L1 seems to be correlated with worse prognosis in the hormone receptor positive subtype. Immune checkpoints inhibitors targeting the PD-1/PD-L1 axis have achieved great response rates in TNBC patients, especially in combination with chemotherapy, making immunotherapy a new treatment option in this scenario. However, the utility of PD-L1 as a predictive biomarker in the rest of BC subtypes remains unclear. In addition, predictive differences have been found in response to immunotherapy depending on the stage of the tumor disease. Therefore, a better understanding of tumor microenvironment, as well as identifying new potential biomarkers or combined index scores, is necessary in order to make a better selection of the subgroups of BC patients who will derive benefit from immune checkpoint inhibitors.

Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

2018 ◽  
Vol 1 (1) ◽  
pp. 28-32
Author(s):  
Piyawat Komolmit
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell Receptor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Immune Checkpoints ◽  
Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals Immune landscape of inflammatory breast cancer suggests vulnerability to immune checkpoint inhibitors

2021 ◽  
Vol 10 (1) ◽  
pp. 1929724
Author(s):  
François Bertucci ◽  
Laurys Boudin ◽  
Pascal Finetti ◽  
Christophe Van Berckelaer ◽  
Peter Van Dam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

scholarly journals Inhibition of the PI3K/mTOR Pathway in Breast Cancer to Enhance Response to Immune Checkpoint Inhibitors in Breast Cancer

2021 ◽  
Vol 22 (10) ◽  
pp. 5207
Author(s):  
Chi Yan ◽  
Jinming Yang ◽  
Nabil Saleh ◽  
Sheau-Chiann Chen ◽  
Gregory D. Ayers ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Mtor Pathway ◽  
Complete Regression ◽  
Mtor Inhibition

Objectives: Inhibition of the PI3K/mTOR pathway suppresses breast cancer (BC) growth, enhances anti-tumor immune responses, and works synergistically with immune checkpoint inhibitors (ICI). The objective here was to identify a subclass of PI3K inhibitors that, when combined with paclitaxel, is effective in enhancing response to ICI. Methods: C57BL/6 mice were orthotopically implanted with syngeneic luminal/triple-negative-like PyMT cells exhibiting high endogenous PI3K activity. Tumor growth in response to treatment with anti-PD-1 + anti-CTLA-4 (ICI), paclitaxel (PTX), and either the PI3Kα-specific inhibitor alpelisib, the pan-PI3K inhibitor copanlisib, or the broad spectrum PI3K/mTOR inhibitor gedatolisib was evaluated in reference to monotherapy or combinations of these therapies. Effects of these therapeutics on intratumoral immune populations were determined by multicolor FACS. Results: Treatment with alpelisib + PTX inhibited PyMT tumor growth and increased tumor-infiltrating granulocytes but did not significantly affect the number of tumor-infiltrating CD8+ T cells and did not synergize with ICI. Copanlisib + PTX + ICI significantly inhibited PyMT growth and increased activation of intratumoral CD8+ T cells as compared to ICI alone, yet did not inhibit tumor growth more than ICI alone. In contrast, gedatolisib + ICI resulted in significantly greater inhibition of tumor growth compared to ICI alone and induced durable dendritic-cell, CD8+ T-cell, and NK-cell responses. Adding PTX to this regimen yielded complete regression in 60% of tumors. Conclusion: PI3K/mTOR inhibition plus PTX heightens response to ICI and may provide a viable therapeutic approach for treatment of metastatic BC.

scholarly journals A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics

2021 ◽  
Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Epidemiological Studies ◽  
Term Survival ◽  
Checkpoint Inhibitor Therapy ◽  
Rational Use Of Antibiotics

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

Understanding resistance to immune checkpoint inhibitors in advanced breast cancer

2021 ◽  
Author(s):  
Paolo Tarantino ◽  
Romualdo Barroso-Sousa ◽  
Ana C. Garrido-Castro ◽  
Sandra S. McAllister ◽  
Jennifer L. Guerriero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Breast

Gastrointestinal Adverse Events Induced by Immune-Checkpoint Inhibitors

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shunichi Yanai ◽  
Yosuke Toya ◽  
Tamotsu Sugai ◽  
Takayuki Matsumoto
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Architectural Distortion ◽  
Management Guidelines ◽  
Crypt Abscess ◽  
Gastrointestinal Adverse Events ◽  
Histopathologic Findings

<b><i>Background:</i></b> As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. <b><i>Summary:</i></b> Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. <b><i>Key Messages:</i></b> Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.

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