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Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors.

ABSTRACT: Thymic epithelial tumors (TETs) are a group of rare thoracic malignancies, including thymic carcinomas (TC) and thymomas (Tm). Autoimmune paraneoplastic diseases are often observed in TETs, especially Tms. To date, chemotherapy is still the standard treatment for advanced disease. Unfortunately, few therapeutic options are available for relapsed/refractory TETs. In the last few years, the deepening of knowledge on thymus' immunobiology and involved altered genetic pathways have laid the foundation for new treatment options in these rare neoplasms. Recently, the immunotherapy revolution has landed in TETs, showing both a dark and light side. Indeed, despite the survival benefit, the occurrence of severe autoimmune treatment-related adverse events has risen crescent uncertainty about the feasibility of immunotherapy in these patients, prone to autoimmunity for their cancer biology. In this review, after summarizing immunobiology and immunopathology of TETs, we discuss available data on immune-checkpoint inhibitors and future perspectives of this therapeutic strategy.

SUBMITTER: Tateo V

PROVIDER: S-EPMC7730788 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors.

Tateo Valentina V Manuzzi Lisa L De Giglio Andrea A Parisi Claudia C Lamberti Giuseppe G Campana Davide D Pantaleo Maria Abbondanza MA

International journal of molecular sciences 20201128 23

Thymic epithelial tumors (TETs) are a group of rare thoracic malignancies, including thymic carcinomas (TC) and thymomas (Tm). Autoimmune paraneoplastic diseases are often observed in TETs, especially Tms. To date, chemotherapy is still the standard treatment for advanced disease. Unfortunately, few therapeutic options are available for relapsed/refractory TETs. In the last few years, the deepening of knowledge on thymus' immunobiology and involved altered genetic pathways have laid the foundati ...[more]

PMID: 33260538

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Project description:BackgroundImmunotherapy offers new hope for cancer patients but presents new medical challenges for healthcare workers in terms of the management of immune-related adverse events (irAEs). The clinical data of two patients with advanced thymoma (T) admitted to the Fujian Cancer Hospital who developed fulminant myocarditis after undergoing immunosuppressant therapy were analyzed retrospectively, and the relevant literature was reviewed. This study aims to examine treatment of thymic epithelial tumors (TETs)-associated immune myocarditis.Case descriptionAn online search was conducted to retrieve relevant full-text articles, and the selected articles were assessed. In total, 13 articles, comprising the data of 113 patients, were included in an analysis to evaluate the efficacy of immunotherapy. Of the 113 patients, 19 had T and 94 had thymic carcinoma (TC). Of the 19 patients with T, 10 (52.6%) achieved a partial response (PR), 8 (42.1%) had stable disease (SD), and 1 (5.3%) had progressive disease (PD). Of the 94 patients with TC, 1 (1.1%) achieved a complete response (CR), 20 (21.3%) achieved a PR, 51 (54.3%) had SD, and 22 (23.4%) had PD. Five articles reported that fulminant myocarditis developed in nine thymic epithelioma patients who were treated with immunosuppressive agents. Two TC patients who presented with fulminant myocarditis were treated with high-dose corticosteroid therapy and underwent pacemaker insertion; none of the patients died of immune myocardial toxicity. However, of the seven T patients who received high-dose corticosteroid therapy and immunoglobulin therapy, and underwent pacemaker implantation, three survived and four died.ConclusionsImmunotherapy has shown promising results in the treatment of patients with refractory or relapsed TETs. Due to their susceptibility to paraneoplastic autoimmunity, TET patients are at a higher risk of developing severe irAEs than patients with other types of cancer. Given the relatively high morbidity and mortality of irAEs, the administration of immune checkpoint inhibitors (ICIs) to treat TETs should be balanced against the clinical response and the precipitation of potentially severe irAEs.

Project description:Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.

Dataset Information

Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors.

Publications

Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors.

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