scholarly journals The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 134
Author(s):  
Anastasia Mpakali ◽  
Efstratios Stratikos
Keyword(s):  
Immune Checkpoint ◽  
Antigen Processing ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Clinical Results ◽  
Therapeutic Benefit ◽  
Complementary Approach ◽  
Intracellular Antigen ◽  
Antigen Processing And Presentation

Recent clinical successes of cancer immunotherapy using immune checkpoint inhibitors (ICIs) are rapidly changing the landscape of cancer treatment. Regardless of initial impressive clinical results though, the therapeutic benefit of ICIs appears to be limited to a subset of patients and tumor types. Recent analyses have revealed that the potency of ICI therapies depends on the efficient presentation of tumor-specific antigens by cancer cells and professional antigen presenting cells. Here, we review current knowledge on the role of antigen presentation in cancer. We focus on intracellular antigen processing and presentation by Major Histocompatibility class I (MHCI) molecules and how it can affect cancer immune evasion. Finally, we discuss the pharmacological tractability of manipulating intracellular antigen processing as a complementary approach to enhance tumor immunogenicity and the effectiveness of ICI immunotherapy.

scholarly journals The Role of Immunotherapy in the Treatment of Advanced Cervical Cancer: Current Status and Future Perspectives

2021 ◽  
Vol 10 (19) ◽  
pp. 4523
Author(s):  
Robert Walsh ◽  
David Tan
Keyword(s):  
Cervical Cancer ◽  
Immune Checkpoint ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Current Status ◽  
Viral Etiology ◽  
Resistance Strategies ◽  
Attractive Option

Cervical cancer remains one of the most common cancers in women around the world however therapeutic options in the advanced and recurrent setting are limited. Immune checkpoint inhibitors (ICI) have been considered an attractive option given the viral etiology of cervical cancer although the majority of patients do not benefit from their use. This review summarises current knowledge and use of immune checkpoint blockade in cervical cancer as well as discussing the challenges faced in their clinical application, namely, the role of biomarker-driven ICI use, potential mechanisms of resistance, strategies to overcome such resistance and additional immunotherapy options beyond ICI.

scholarly journals The Role of Molecular Profiling to Predict the Response to Immune Checkpoint Inhibitors in Lung Cancer

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 201 ◽  
Author(s):  
Courèche Kaderbhaï ◽  
Zoé Tharin ◽  
François Ghiringhelli
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Surrogate Marker ◽  
Dna And Rna ◽  
Tumor Mutational Burden ◽  
Tumor Expression

Immune checkpoint inhibitors radically changed the treatment of patients with non-small cell lung cancer (NSCLC). However, only one-quarter of patients benefit from these new therapies when used as monotherapy. The assessment of Program Death Ligand-1 (PD-L1) tumor expression by immunohistochemistry is used to select potential responder patients, but this not an optimal marker since it does not predict the absence of anti PD-1 efficacy. Despite this shortcoming, PD-L1 remains the gold standard biomarker in many studies and the only biomarker available for clinicians. In addition to histological markers, transcriptomic and exome analyses have revealed potential biomarkers requiring further confirmation. Recently, tumor mutational burden has emerged as a good surrogate marker of outcome. In this review we will detail current knowledge on DNA and RNA related biomarkers.

Gastroenteropancreatic Neuroendocrine Neoplasms (GEP NENs) : The Role of Checkpoint Inhibitors

2022 ◽  
Vol 22 ◽  
Author(s):  
Giulia Arrivi ◽  
Nicola Fazio
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Response Assessment ◽  
Neuroendocrine Neoplasms ◽  
Precision Oncology ◽  
Disease Characteristics

Background: The treatment options for GEP-NENs includes various drugs and is based on grading, morphology and location of the primary Objective: The aim of our work is to investigate the clinical impact of new immune checkpoint inhibitors in order to define a new possible strategy of use within GEP-NENs. Method: A scientific literature search from 2015 to January 2020 was performed by using PubMed and Embase: reviews and prospective or retrospective studies with a minimum of twenty patients were selected; conference proceedings were included Results: several studies have been conducted to assess the role of immune checkpoint inhibitors in NENs, but nowadays the current knowledge in this field is mainly based on a phase I-II studies. Immunotherapy showed limited antitumor activity, but higher response rate was reported in poor-differentiated neuroendocrine tumors. No specific biomarkers were identified for patient selection and response assessment Conclusion: Immunotherapy appears as a powerful possibility to help our patients, but nowadays we see many gaps in this field. We must balance therapeutic possibility offered by precision oncology with the understanding the limitations of application of testing and treatment in clinical practice. Future efforts should focus on research of the best patients to candidate for immunotherapy in term of disease characteristics and previous treatments, and how to select them with accurate biomarkers.

Clinical efficacy of immune checkpoint inhibitors in patients with brain metastases

Immunotherapy ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 419-432
Author(s):  
Vincenzo Di Nunno ◽  
Giacomo Nuvola ◽  
Mirta Mosca ◽  
Ilaria Maggio ◽  
Lidia Gatto ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Standard Treatment ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Clinical Role ◽  
Negative Prognostic Factor ◽  
Solid Malignancies

Brain metastases (BMs) represent a negative prognostic factor for patients with solid malignancies. BMs are generally approached with loco-regional treatments and the blood–brain barrier limits the efficacy of some systemic drugs. The aim of this review is to summarize current knowledge about the role of immune checkpoint inhibitors for the management of brain metastases in patients with solid malignancies. We performed a review of available literature. Immune checkpoint inhibitors represent the standard treatment for several advanced solid malignancies. However, with the exception of melanoma their clinical role in other solid malignancies is not completely clear due to the exclusion of patients with BM from approval clinical trials. Immune-checkpoint inhibitors may be an effective treatment of brain metastases of melanoma while their clinical role on brain metastases from other solid malignancies is uncertain.

scholarly journals Current Progress and Future Perspectives of Immune Checkpoint in Cancer and Infectious Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Cai ◽  
Huajie Zhan ◽  
Yuguang Ye ◽  
Jinjin Yang ◽  
Minghui Zhang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Checkpoint ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints ◽  
Microbial Infection ◽  
Antiviral Immune Response

The inhibitory regulators, known as immune checkpoints, prevent overreaction of the immune system, avoid normal tissue damage, and maintain immune homeostasis during the antimicrobial or antiviral immune response. Unfortunately, cancer cells can mimic the ligands of immune checkpoints to evade immune surveillance. Application of immune checkpoint blockade can help dampen the ligands expressed on cancer cells, reverse the exhaustion status of effector T cells, and reinvigorate the antitumor function. Here, we briefly introduce the structure, expression, signaling pathway, and targeted drugs of several inhibitory immune checkpoints (PD-1/PD-L1, CTLA-4, TIM-3, LAG-3, VISTA, and IDO1). And we summarize the application of immune checkpoint inhibitors in tumors, such as single agent and combination therapy and adverse reactions. At the same time, we further discussed the correlation between immune checkpoints and microorganisms and the role of immune checkpoints in microbial-infection diseases. This review focused on the current knowledge about the role of the immune checkpoints will help in applying immune checkpoints for clinical therapy of cancer and other diseases.

Predictive markers of immune response in glioblastoma: hopes and facts

2020 ◽  
Vol 16 (15) ◽  
pp. 1053-1063 ◽  
Author(s):  
Vincenzo Di Nunno ◽  
Enrico Franceschi ◽  
Lidia Gatto ◽  
Stefania Bartolini ◽  
Alba Ariela Brandes
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Predictive Markers ◽  
Advanced Solid Tumors ◽  
Critical Importance

Immune-checkpoint inhibitors (ICI) represent a concrete hope for patients with advanced solid tumors. Indeed, patients responding to these agents may experience a long-lasting response. Recently, results of interventional clinical trials investigated the role of ICIs in patients with glioblastoma. Results of these studies suggested that only a small percentage of these patients could benefit from these agents. Research of predictive markers assumes a critical importance to adequately select patients likely to benefit from ICIs. Molecular and clinical variables associated to tumors and patients have been evaluated as potential predictive markers. Main aim of the current work is to summarize and critically evaluate current knowledge in this field.

scholarly journals Immune Check Point Inhibitors in Primary Cutaneous T-Cell Lymphomas: Biologic Rationale, Clinical Results and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Gabriele Roccuzzo ◽  
Silvia Giordano ◽  
Paolo Fava ◽  
Alessandro Pileri ◽  
Alba Guglielmo ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Published Data ◽  
Immune Checkpoint Molecules ◽  
T Cell Lymphomas ◽  
Cutaneous Lymphomas

Primary cutaneous T-cell lymphomas (PCTCL) are the most common types of cutaneous lymphomas, with Mycosis fungoides as the most frequent subtype. Besides early stages which usually have a good prognosis, advanced stages remain a great therapeutic challenge with low survival rates. To date, none of the currently available therapeutic options have significantly improved the outcomes of advanced cutaneous lymphomas. Recent studies have demonstrated that immune-checkpoint molecules, such as PD-1 and CTLA-4, play part in the proliferation pathways of neoplastic T-cells, as well as in other tumors. Hence, the potential role of immune-checkpoint-inhibitors in treating cutaneous lymphomas has been investigated in the last years. Herein, we outline the current knowledge regarding the role of immune-checkpoint molecules in PCTCL, their signaling pathways, microenvironment and therapeutic inhibition rationale. Moreover, we review the published data on immunotherapies in PCTCL and summarize the currently ongoing clinical trials in this field.

The Role of PET/CT in the Era of Immune Checkpoint Inhibitors: State of Art

2020 ◽  
Vol 13 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Angelo Castello ◽  
Egesta Lopci
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Evaluation Criteria ◽  
Advanced Melanoma ◽  
Response Criteria ◽  
Response Evaluation ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Background: Immune checkpoint inhibitors (ICI) have achieved astonishing results and improved overall survival (OS) in several types of malignancies, including advanced melanoma. However, due to a peculiar type of anti-cancer activity provided by these drugs, the response patterns during ICI treatment are completely different from that with “old” chemotherapeutic agents. Objective: To provide an overview of the available literature and potentials of 18F-FDG PET/CT in advanced melanoma during the course of therapy with ICI in the context of treatment response evaluation. Methods: Morphologic criteria, expressed by Response Evaluation Criteria in Solid Tumors (RECIST), immune-related response criteria (irRC), irRECIST, and, more recently, immune-RECIST (iRECIST), along with response criteria based on the metabolic parameters with 18F-Fluorodeoxyglucose (18FFDG), have been explored. Results: To overcome the limits of traditional response criteria, new metabolic response criteria have been introduced on time and are being continuously updated, such as the PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy (PECRIT), the PET Response Evaluation Criteria for Immunotherapy (PERCIMT), and “immunotherapy-modified” PET Response Criteria in Solid Tumors (imPERCIST). The introduction of new PET radiotracers, based on monoclonal antibodies combined with radioactive elements (“immune-PET”), are of great interest. Conclusion: Although the role of 18F-FDG PET/CT in malignant melanoma has been widely validated for detecting distant metastases and recurrences, evidences in course of ICI are still scarce and larger multicenter clinical trials are needed.

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