Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets.

Molecular pathways involved in COVID-19 and potential pathway-based therapeutic targets

An increasing number of studies have shown that immunotherapy serves a significant role in treating colorectal cancer (CRC) and has become a hotspot. However, few studies used the bibliometric method to analyze this field comprehensively. This study collected 1,899 records of CRC immunotherapy from 2012 to October 31, 2021, and used CiteSpace to analyze regions, institutions, journals, authors, and keywords to predict the latest trends in CRC immunotherapy research. The United States and China, contributing more than 60% of publications, were the main drivers in this field. Sun Yat-sen University was the most active institution, while the National Cancer Institute had the highest frequency of citations. Most publications were published in the Journal for Immunotherapy of Cancer. Adam E Snook was the most prolific writer, while Dung T. Le was the most commonly co-cited author. “T cell”, “MMI” and “PD-1blocked” were the most widely studied aspects of CRC immunotherapy. “Immune checkpoint inhibitor”, “combination therapy”, “drug therapy” and “liver metastases” were current research hotspots. “Tumor microenvironment”, “neutrophils”, “tumor-associated macrophages”, and “suppressor cell” have emerged as research hotspots in recent years. “Gut microbiota”, “nanoparticle” and “tumor mutational burden” as recently emerged frontiers of research that should be closely monitored.

Visual Analysis of Colorectal Cancer Immunotherapy: A Bibliometric Analysis From 2012 to 2021

Photoelectrochemical biosensing platforms for tumor marker detection

During this last decade, adoptive transfer of T lymphocytes genetically modified to express chimeric antigen receptors (CARs) emerged as a valuable therapeutic strategy in hematological cancers. However, this immunotherapy has demonstrated limited efficacy in solid tumors. The main obstacle encountered by CAR-T cells in solid malignancies is the immunosuppressive tumor microenvironment (TME). The TME impedes tumor trafficking and penetration of T lymphocytes and installs an immunosuppressive milieu by producing suppressive soluble factors and by overexpressing negative immune checkpoints. In order to overcome these hurdles, new CAR-T cells engineering strategies were designed, to potentiate tumor recognition and infiltration and anti-cancer activity in the hostile TME. In this review, we provide an overview of the major mechanisms used by tumor cells to evade immune defenses and we critically expose the most optimistic engineering strategies to make CAR-T cell therapy a solid option for solid tumors.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.830292/pdf

Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment

Programmed death protein 1 (PD1) is a common immunosuppressive member on the surface of T cells and plays an imperative part in downregulating the immune system and advancing self-tolerance. Its ligand programmed cell death ligand 1 (PDL1) is overexpressed on the surface of malignant tumor cells, where it binds to PD1, inhibits the proliferation of PD1-positive cells, and participates in the immune evasion of tumors leading to treatment failure. The PD1/PDL1-based pathway is of great value in immunotherapy of cancer and has become an important immune checkpoint in recent years, so understanding the mechanism of PD1/PDL1 action is of great significance for combined immunotherapy and patient prognosis. The inhibitors of PD1/PDL1 have shown clinical efficacy in many tumors, for example, blockade of PD1 or PDL1 with specific antibodies enhances T cell responses and mediates antitumor activity. However, some patients are prone to develop drug resistance, resulting in poor treatment outcomes, which is rooted in the insensitivity of patients to targeted inhibitors. In this paper, we reviewed the mechanism and application of PD1/PDL1 checkpoint inhibitors in tumor immunotherapy. We hope that in the future, promising combination therapy regimens can be developed to allow immunotherapeutic tools to play an important role in tumor treatment. We also discuss the safety issues of immunotherapy and further reflect on the effectiveness of the treatment and the side effects it brings.

/pdf/pd-1-pd-l1-checkpoint-inhibitors-in-tumor-immunotherapy-2vn6e21cau.pdf

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

Telomerase and micro-RNAs (miRNAs) are simultaneously upregulated in a variety of tumor cells and have emerged as promising tumor markers. However, sensitive detection of telomerase and miRNAs in situ remains a great challenge due to their low expression levels. Here, we designed a Boolean logic "AND" signal amplification strategy based on functionalized ordered mesoporous nanoparticles (FOMNs) to achieve ultrasensitive detection of telomerase and miR-21 in living tumor cells. Briefly, the strategy uses telomerase as an input to enable the release of DNA3-ROX-BHQ hairpins by making the wrapping DNA1 form a DNA-a hairpin with the joint participation of dNTPs. Subsequently, DNA2-Ag, DNA3-ROX-BHQ, and the second input miR-21 participated in hybridization chain reaction to amplify fluorescence and Raman signals. Experimental results showed the intensity of output dual signals relevant to the expression levels of telomerase and miR-21. The Ag nanoparticles (AgNPs) not only enhanced the fluorescence signals but also allowed to obtain more sensitive Raman signals. Therefore, even if expression of tumor markers is at a low level, the FOMN-based dual-signal logic operation strategy can still achieve sensitive detection of telomerase and miR-21 in situ. Furthermore, FOMNs can detect miR-21 expression levels in a short time. Consequently, this strategy has a potential clinical application value in detection of tumor markers and the assessment of tumor treatment efficacy.

Ultrasensitive Dual-Signal Detection of Telomerase and MiR-21 Based on Boolean Logic Operations.

COVID-19 pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has ravaged the world, resulting in an alarming number of infections and deaths, and the number continues to increase. The pathogenesis caused by the novel coronavirus was found to be a disruption of the pro-inflammatory/anti-inflammatory response. Due to the lack of effective treatments, different strategies and treatment methods are still being researched, with the use of vaccines to make the body immune becoming the most effective means of prevention. Antiviral drugs and respiratory support are often used clinically as needed, but are not yet sufficient to alleviate the cytokine storm (CS) and systemic inflammatory response syndrome. How to neutralize the cytokine storm and inhibit excessive immune cell activation becomes the key to treating neocoronavirus pneumonia. Immunotherapy through the application of hormones and monoclonal antibodies can alleviate the immune imbalance, but the clinical effectiveness and side effects remain controversial. This article reviews the pathogenesis of neocoronavirus pneumonia and discusses the immunomodulatory therapies currently applied to COVID-19. We aim to give some conceptual thought to the prevention and immunotherapy of neocoronavirus pneumonia.

/pdf/immunotherapy-summary-for-cytokine-storm-in-covid-19-rw1vnw2ogf.pdf

Zichao Chen

Papers

PD-1/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy

Ultrasensitive Dual-Signal Detection of Telomerase and MiR-21 Based on Boolean Logic Operations.

Immunotherapy Summary for Cytokine Storm in COVID-19.