Complete Metabolic Response to Combined Immune Checkpoint Inhibition after Progression of Metastatic Colorectal Cancer on Pembrolizumab: A Case Report DOI Open Access
Carolin Krekeler, Klaus Wethmar, Jan‐Henrik Mikesch

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12056 - 12056

Published: July 27, 2023

DNA mismatch repair deficient (dMMR) and microsatellite instable (MSI) metastatic colorectal cancer (mCRC) can be successfully treated with FDA- EMA-approved immune checkpoint inhibitors (ICI) pembrolizumab nivolumab (as single agents targeting the anti-programmed cell death protein-1 (PD-1)) or combinations of a PD-1 inhibitor ipilimumab, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-targeting antibody. The best treatment strategy beyond progression on single-agent ICI therapy remains unclear. Here, we present case 63-year-old male Lynch-syndrome-associated, instability-high (MSI-H) mCRC who achieved rapid normalization his tumor markers complete metabolic remission (CMR), currently lasting for ten months, sequential combination ipilimumab followed by maintenance after anti-PD-1 therapy. was well-tolerated, no immune-related adverse events occurred. To our knowledge, this is first sustained in an MSI-H patient initially progressing Thus, dMMR patients might benefit from regimens even long-term responses. However, further sophistication clinical algorithms MSI-mCRC urgently needed.

Language: Английский

Advances in dendritic cell vaccination therapy of cancer DOI Open Access
Sajad Najafi, Keywan Mortezaee

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114954 - 114954

Published: May 29, 2023

Traditionally, vaccines have helped eradication of several infectious diseases and also saved millions lives in the human history. Those prophylactic acted through inducing immune responses against a live attenuated, killed organism or antigenic subunits to protect recipient real infection caused by pathogenic microorganism. Nevertheless, development anticancer as valuable targets health has faced challenges requires further optimizations. Dendritic cells (DCs) are most potent antigen presenting (APCs) that play essential roles tumor immunotherapies induction CD8+ T cell immunity. Accordingly, various strategies been tested employ DCs therapeutic for exploiting their activity cells. Application whole purified/recombinant peptides common approaches pulsing DCs, which then injected back into patients. Although some hopeful results reported number DC animal clinical trials cancer patients, such still inefficient require optimization. Failure vaccination is postulated due immunosuppressive microenvironment (TME), overexpression checkpoint proteins, suboptimal avidity tumor-associated (TAA)-specific lymphocytes, lack appropriate adjuvants. In this review, we an overview current experiments evaluated efficacy well focusing on improve potential including combination therapy with inhibitors (ICIs).

Language: Английский

Citations

53
The role of microRNAs in the pathophysiology of human central nervous system: A focus on neurodegenerative diseases DOI
Delsuz Rezaee,

Fatemeh Saadatpour,

Nayyereh Akbari

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102090 - 102090

Published: Oct. 11, 2023

Language: Английский

Citations

44
Extracellular vesicle–based drug delivery in cancer immunotherapy DOI Open Access
Sajad Najafi, Jamal Majidpoor, Keywan Mortezaee

et al.

Drug Delivery and Translational Research, Journal Year: 2023, Volume and Issue: 13(11), P. 2790 - 2806

Published: June 1, 2023

Language: Английский

Citations

38
The role of microRNA-185 in the pathogenesis of human diseases: A focus on cancer DOI Open Access
Safoora Pordel,

Motahare Khorrami,

Fatemeh Saadatpour

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154729 - 154729

Published: Aug. 16, 2023

Language: Английский

Citations

30
Mechanisms of CD8+ T cell exclusion and dysfunction in cancer resistance to anti-PD-(L)1 DOI Creative Commons
Keywan Mortezaee, Jamal Majidpoor

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114824 - 114824

Published: May 2, 2023

CD8+ T cells are the front-line defensive against cancer. Reduced infiltration and effector function of occurs in cancer is contributed to defective immunity immunotherapy resistance. Exclusion exhaustion two key factors associated with reduced durability immune checkpoint inhibitor (ICI) therapy. Initially activated upon exposure chronic antigen stimulation or immunosuppressive tumor microenvironment (TME) acquire a hyporesponsive state that progressively lose their function. Thus, strategy look for cell Targeting such can define promising supplementary approach patients receiving anti-programmed death-1 receptor (PD-1)/anti-programmed death-ligand 1 (PD-L1) Recently, bispecific antibodies developed PD-(L)1 dominant factor within TME, representing higher safety profile exerting more desired outcomes. The focus this review discuss about promoters deficient addressing ICI

Language: Английский

Citations

25
WNT/β-catenin regulatory roles on PD-(L)1 and immunotherapy responses DOI Creative Commons
Keywan Mortezaee

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 27, 2024

Abstract Dysregulation of WNT/β-catenin is a hallmark many cancer types and key mediator metastasis in solid tumors. Overactive β-catenin signaling hampers dendritic cell (DC) recruitment, promotes CD8 + T exclusion increases the population regulatory cells (Tregs). The activity also induces expression programmed death-ligand 1 (PD-L1) on tumor death-1 (PD-1) upregulation. Increased after anti-PD-1 therapy indicative possible implication this bypassing immune checkpoint inhibitor (ICI) therapy. This review aimed at giving comprehensive overview roles PD-1/PD-L1 axis ecosystem, discussing about mechanistic events contributed to WNT/β-catenin-mediated bypass ICI therapy, representing inhibitors as promising combinatory regimen go with anti-PD-(L)1 immunotherapy. Ideas presented imply synergistic efficacy such combination rendering durable anti-tumor immunity.

Language: Английский

Citations

15
The emerging and challenging role of PD-L1 in patients with gynecological cancers: An updating review with clinico-pathological considerations DOI Creative Commons
Angela Santoro, Giuseppe Angelico, Frediano Inzani

et al.

Gynecologic Oncology, Journal Year: 2024, Volume and Issue: 184, P. 57 - 66

Published: Jan. 30, 2024

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block PD-1/PD-L1 axis. These have demonstrated their ability enhance immune response by prompting T cells identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on lymphocytes, B antigen-presenting considered key inhibitory checkpoint involved cancer regulation. immunohistochemical expression gynecological malignancies extremely variable based tumor stage molecular subtypes. As result, class monoclonal antibodies targeting PD-1 receptor PD-L1, known as inhibitors, found successful application clinical settings. In practice, standard method for identifying suitable candidates inhibitor therapy involves assessment tissues. The most commonly used assays trials are SP142, 28-8, 22C3, SP263, each which rigorously validated specific platforms. Gynecologic cancers encompass wide spectrum originating from ovaries, uterus, cervix, vulva. neoplasms shown immunotherapy appears be influenced genetic profiles, including factors such mismatch repair status, mutational burden, expression. present paper, an extensive review various gynecologic types discussed, providing guide pathological reporting.

Language: Английский

Citations

14
microRNA-184 in the landscape of human malignancies: a review to roles and clinical significance DOI Creative Commons
Mehdi Fattahi, Delsuz Rezaee,

Fatemeh Fakhari

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Nov. 24, 2023

Abstract MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) with short length 19–22 nucleotides. miRNAs posttranscriptional regulators gene expression involved in various biological processes like cell growth, apoptosis, and angiogenesis. miR-184 is well-studied miRNA, for which most studies report its downregulation cancer cells tissues experiments support role as tumor suppressor inhibiting malignant behaviors vitro vivo. To exert functions, affects some signaling pathways tumorigenesis Wnt β-catenin, AKT/mTORC1 pathway, oncogenic factors (e.g., c-Myc) or apoptotic proteins, such Bcl-2. Interestingly, clinical investigations have shown good performance prognostic/diagnostic biomarker cancers. Additionally, exogenous xenograft animal suggest it therapeutic anticancer target. In this review, we outline the that evaluated roles well significance.

Language: Английский

Citations

22
Indoleamine 2,3-dioxygenase 1 in circumventing checkpoint inhibitor responses: Updated DOI

Arian Charehjoo,

Jamal Majidpoor, Keywan Mortezaee

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 118, P. 110032 - 110032

Published: March 17, 2023

Language: Английский

Citations

16
Tumor-educated platelets DOI
Sajad Najafi, Yahya Asemani, Jamal Majidpoor

et al.

Clinica Chimica Acta, Journal Year: 2023, Volume and Issue: 552, P. 117690 - 117690

Published: Dec. 4, 2023

Language: Английский

Citations

16