scholarly journals Revolutionizing Cancer Therapeutics: Molecular Pathways and Techniques in Cancer Immunotherapy

2017 ◽  
Vol 10 (1) ◽  
Author(s):  
Bea Co
Keyword(s):  
T Cells ◽  
Literature Review ◽  
Cancer Immunotherapy ◽  
Checkpoint Inhibitors ◽  
Cancer Therapeutics ◽  
Molecular Pathways ◽  
Cancer Therapies ◽  
Engineered T Cells ◽  
Il Y A ◽  
Cellules T

Contrary to conventional cancer therapies, immunotherapy manipulates an individual’s body cells to fight cancer, enhancing the active and dynamic immune interactions between the tumour and host. Cancer immunotherapy provides evidence of success through a variety of treatment approaches. Utilizing T-cells and antibodies, immunotherapy strategies such as T-cell engaging bodies, checkpoint inhibitors and engineered T-cells have significantly increased the chance of survival for many cancer patients. The combinations of these immunotherapies have also granted greater success in the elimination of tumour cells. Immunotherapy breakthroughs have the potential to have a lasting impact on cancer treatment. This literature review sheds light on the importance in further research for cancer immunotherapy and a glimpse at all of its powerful results. Contrairement aux méthodes conventionnelles de traitement anti-cancereux, l’immunothérapie manipule les cellules somatiques d’un patient pour battre contre le cancer, améliorant les interactions immunitaires actives et dynamiques entre la tumeur et l’hôte. Par une variété de méthodes de traitement, il y a une abondance de preuve qui montre le succès exceptionnel dans l’utilisation de l’immunothérapie contre le cancer. Les stratégies immunothérapeutiques, par exemple l’utilisation des anticorps bispécifiques qui engagent les cellules T, des inhibiteurs de checkpoint et les cellules T ingénierées, ont augmenté considérablement la chance de survie pour beaucoup de patients frappés par le cancer. Les combinaisons de ces immunothérapies ont aussi permis des grands succès avec l’élimination des cellules cancéreux. L’immunothérapie a mené à des nombreuses percées qui vont avoir un impact durable sur le traitement de cancer. Elle fournit continuellement des nouvelles découvertes qui ont déjà commencées de révolutionner les thérapies de cancer. Cette revue littéraire éclaircit l’importance de la continuation des recherches concernant l’immunothérapie pout le cancer et donne aussi un aperçu de tous ses résultats puissants. 

Cancer Immunology and CAR-T Cells: A Turning Point Therapeutic Approach in Colorectal Carcinoma with clinical insight

2020 ◽  
Vol 20 ◽  
Author(s):  
Suman K Ray ◽  
Yamini Meshram ◽  
Sukhes Mukherjee
Keyword(s):  
T Cells ◽  
Colorectal Carcinoma ◽  
Cancer Immunotherapy ◽  
Clinical Evidence ◽  
Ex Vivo ◽  
Clinical Success ◽  
Recent Decade ◽  
Molecular Immunology ◽  
Car T ◽  
Engineered T Cells

: Cancer immunotherapy endeavours in harnessing delicate strength and specificity of immune system for therapy of different malignancies including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies including colorectal carcinoma in a recent decade. Despite considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.

Structure and functions of T-cell immunoglobulin-domain and mucin- domain protein 3 in cancer

2021 ◽  
Vol 28 ◽  
Author(s):  
Xinjie Lu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Intracellular Signaling ◽  
Checkpoint Inhibitors ◽  
Cell Types ◽  
Structural Features ◽  
Type I ◽  
Potential Biomarker ◽  
Tim Proteins

Background: T-cell immunoglobulin (Ig)-domain and mucin-domain (TIM) proteins represent a family of receptors expressed on T-cells that play essential cellular immunity roles. The TIM proteins span across the membrane belonging to type I transmembrane proteins. The N terminus contains an Ig-like V-type domain and a Ser/Thr-rich mucin stalk as a co-inhibitory receptor. The C-terminal tail oriented toward the cytosol predominantly mediates intracellular signaling. Methods: This review discusses the structural features and functions of TIM-3, specifically on its role in mediating immune responses in different cell types, and the rationale for TIM-3-targeted cancer immunotherapy. Results: TIM-3 has gained significant importance to be a potential biomarker in cancer immunotherapy. It has been shown that blockade with checkpoint inhibitors promotes anti-tumor immunity and inhibits tumor growth in several preclinical tumor models. Conclusion: TIM-3 is an immune regulating molecule expressed on several cell types, including IFNγ-producing T-cells, FoxP3+ Treg cells, and innate immune cells. The roles of TIM-3 in immunosuppression support its merit as a target for cancer immunotherapy.

scholarly journals Autoimmunity linked protein phosphatase PTPN22 as a target for cancer immunotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e001439 ◽  
Author(s):  
Rafael Cubas ◽  
Zia Khan ◽  
Qian Gong ◽  
Marina Moskalenko ◽  
Huizhong Xiong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Phosphatase Activity ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Therapeutic Option ◽  
Interleukin 2 ◽  
Cell Functions ◽  
Increased Risk

BackgroundCancer immunotherapy has evolved from interferon-alpha (IFNα) and interleukin-2 in the 1980s to CTLA-4 and PD-1/PD-L1 checkpoint inhibitors (CPIs), the latter highlighting the importance of enhancing T-cell functions. While the search for novel immunomodulatory pathways continues, combination therapies augmenting multiple pathways can also increase efficacy. The association of autoimmune-related adverse events with clinical efficacy following CPI treatment has been inferred and suggests that breaking tolerance thresholds associated with autoimmunity may affect host immune responses for effective cancer immunotherapy.ResultsHere, we show that loss of autoimmune associated PTPN22, a key desensitization node for multiple signaling pathways, including IFNα receptor (IFNAR) and T-cell receptor, can augment tumor responses. Implantation of syngeneic tumors in Ptpn22-/- mice led to expansion and activation of peripheral and intratumoral T cells and, in turn, spontaneous tumor regression as well as enhanced responses in combination with anti-PD-L1 treatment. Using genetically modified mice expressing a catalytically inactive PTPN22 or the autoimmunity-associated human single-nucleotide polymorphism variant, augmentation of antitumor immunity was dependent on PTPN22 phosphatase activity and partially on its adaptor functions. Further, antitumor responses were dependent on both CD4+ and CD8+T cells and, in part, IFNAR function. Finally, we demonstrate that the autoimmune susceptibility Ptpn22(C1858T) variant is associated with lower risk of developing non-melanoma skin cancers, improved overall survival and increased risk for development of hyperthyroidism or hypothyroidism following atezolizumab (anti-PD-L1) treatment.ConclusionsTogether, these data suggest that inhibition of PTPN22 phosphatase activity may provide an effective therapeutic option for cancer immunotherapy and that exploring genetic variants that shift immune tolerance thresholds may serve as a paradigm for finding new cancer immunotherapy targets.

The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells

2019 ◽  
Vol 84 (7) ◽  
pp. 695-710 ◽  
Author(s):  
P. M. Gershovich ◽  
A. V. Karabelskii ◽  
A. B. Ulitin ◽  
R. A. Ivanov
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Checkpoint Inhibitors ◽  
Genetically Modified

Graded potency of chimeric antigen receptor (CAR)-engineered T cells for cancer immunotherapy.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3022-3022
Author(s):  
Michel Sadelain ◽  
Maud Condomines ◽  
Zeguo Zhao ◽  
Renier J. Brentjens ◽  
Isabelle Riviere
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Engineered T Cells

scholarly journals A Systematic Review of the Tumor-Infiltrating CD8+ T-Cells/PD-L1 Axis in High-Grade Glial Tumors: Toward Personalized Immuno-Oncology

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahdi Abdoli Shadbad ◽  
Zahra Asadzadeh ◽  
Negar Hosseinkhani ◽  
Afshin Derakhshani ◽  
Nazila Alizadeh ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Cancer Therapies ◽  
High Grade ◽  
Glial Tumors ◽  
Anti Cancer ◽  
The Impact

Based on preclinical findings, programmed death-ligand 1 (PD-L1) can substantially attenuate CD8+ T-cell-mediated anti-tumoral immune responses. However, clinical studies have reported controversial results regarding the significance of the tumor-infiltrating CD8+ T-cells/PD-L1 axis on the clinical picture and the response rate of patients with high-grade glial tumors to anti-cancer therapies. Herein, we conducted a systematic review according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements to clarify the clinical significance of the tumor-infiltrating CD8+ T-cells/PD-L1 axis and elucidate the impact of this axis on the response rate of affected patients to anti-cancer therapies. Indeed, a better understanding of the impact of this axis on the response rate of affected patients to anti-cancer therapies can provide valuable insights to address the futile response rate of immune checkpoint inhibitors in patients with high-grade glial tumors. For this purpose, we systematically searched Scopus, Web of Science, Embase, and PubMed to obtain peer-reviewed studies published before 1 January 2021. We have observed that PD-L1 overexpression can be associated with the inferior prognosis of glioblastoma patients who have not been exposed to chemo-radiotherapy. Besides, exposure to anti-cancer therapies, e.g., chemo-radiotherapy, can up-regulate inhibitory immune checkpoint molecules in tumor-infiltrating CD8+ T-cells. Therefore, unlike unexposed patients, increased tumor-infiltrating CD8+ T-cells in anti-cancer therapy-exposed tumoral tissues can be associated with the inferior prognosis of affected patients. Because various inhibitory immune checkpoints can regulate anti-tumoral immune responses, the single-cell sequencing of the cells residing in the tumor microenvironment can provide valuable insights into the expression patterns of inhibitory immune checkpoints in the tumor micromovement. Thus, administrating immune checkpoint inhibitors based on the data from the single-cell sequencing of these cells can increase patients’ response rates, decrease the risk of immune-related adverse events development, prevent immune-resistance development, and reduce the risk of tumor recurrence.

scholarly journals Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy

Cell Research ◽  
2020 ◽  
Vol 30 (11) ◽  
pp. 966-979 ◽  
Author(s):  
Mengze Lv ◽  
Meixia Chen ◽  
Rui Zhang ◽  
Wen Zhang ◽  
Chenguang Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Cancer Therapeutics ◽  
Type I

Abstract CD8+ T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1, an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance. Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes. Unfortunately, only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity. Antitumor immunity depends on the activation of the cGAS-STING pathway, as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells (DCs) to activate CD8+ T cells. STING agonists also enhance natural killer (NK) cells to mediate the clearance of CD8+ T cell-resistant tumors. Therefore STING agonists have been intensively sought after. We previously discovered that manganese (Mn) is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING. Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors. Mn-insufficient mice had significantly enhanced tumor growth and metastasis, with greatly reduced tumor-infiltrating CD8+ T cells. Mechanically, Mn2+ promoted DC and macrophage maturation and tumor-specific antigen presentation, augmented CD8+ T cell differentiation, activation and NK cell activation, and increased memory CD8+ T cells. Combining Mn2+ with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice. Importantly, a completed phase 1 clinical trial with the combined regimen of Mn2+ and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors. We propose that this combination strategy warrants further clinical translation.

Overcoming key challenges in cancer immunotherapy with engineered T cells

2020 ◽  
Vol 32 (5) ◽  
pp. 398-407
Author(s):  
Silvia Arcangeli ◽  
Katrin Mestermann ◽  
Justus Weber ◽  
Chiara Bonini ◽  
Monica Casucci ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Engineered T Cells

scholarly journals Safety Strategies of Genetically Engineered T Cells in Cancer Immunotherapy

2018 ◽  
Vol 24 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Yan-Bei Ren ◽  
Shang-Jun Sun ◽  
Shuang-Yin Han
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Suicide Gene ◽  
Cell Receptor ◽  
Genetically Engineered ◽  
Great Promise ◽  
T Cell Therapy ◽  
Treatment Regimens ◽  
Engineered T Cells

T-cell therapy using genetically engineered T cells modified with either T cell receptor or chimeric antigen receptor holds great promise for cancer immunotherapy. The concerns about its toxicities still remain despite recent successes in clinical trials. Temporal and spatial control of the engineered therapeutic T cells may improve the safety profile of these treatment regimens. To achieve these goals, numerous approaches have been tested and utilized including the incorporation of a suicide gene, the switch-mediated activation, the combinatorial antigen recognition, etc. This review will summarize the toxicities caused by engineered T cells and novel strategies to overcome them.

Sign in / Sign up

Export Citation Format

Share Document