Polyglandular Autoimmune Syndrome Triggered after CTLA-4 and PD-1L Immunotherapy Treatment

Juan Luís Fernández-Morera ,Judit Romano-García,Alfredo Renilla González ,Carmen Elena Calvo Rodríguez

doi:10.3390/reports4010001

Juan Luís Fernández-Morera , Judit Romano-García + Show 2 more

Open Access

https://doi.org/10.3390/reports4010001

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Abstract

Background: CTLA-4 and PD-1L are novel immune checkpoint targets for cancer treatment with specific side effects such as autoimmune diseases. Less frequently, the presence of several autoimmune diseases in the same patient has been described. In this communication, we illustrate the case of a 45-year-old patient with a previous diagnosis of advanced cancer that, after starting treatment with this immunotherapy, developed in the following months autoimmune diabetes, lymphocytic hypophysitis, and a Hashimoto thyroiditis in an abrupt and intense manner that would correspond to an autoimmune polyglandular disease. Discussion: The activation of autoimmunity and associated diseases is increasing in parallel with augmented indication of these immunotherapeutic treatments in cancer patients. A closer follow-up of these patients could be necessary for an optimal approach to this type of pathology. Conclusions: Different autoimmune diseases can converge in the same patient when immunotherapy for cancer is indicated to boost immune response against tumor, caused by altering immune tolerance.

Highlights

Immune checkpoint inhibitors (ICIs) belong to a novel cluster of anticancer drugs targeting T-cell proteins implicated in the activation of immune response against malignancies
We illustrate the case of a 45-year-old patient with a previous diagnosis of advanced cancer that, after starting treatment with this immunotherapy, developed in the following months autoimmune diabetes, lymphocytic hypophysitis, and a Hashimoto thyroiditis in an abrupt and intense manner that would correspond to an autoimmune polyglandular disease
CTLA-4 interacts with non-MHC receptors during antigenic presentation to inhibit the activation of T lymphocytes [4] (Figure 1), whereas PD-1L is frequently overexpressed in tumor cells, facilitating their survival after response of the immune system, and favoring tumor progression [5] (Figure 2)

Summary

Introduction

Immune checkpoint inhibitors (ICIs) belong to a novel cluster of anticancer drugs targeting T-cell proteins implicated in the activation of immune response against malignancies Their use in clinical practice has been a milestone in current cancer treatment. CTLA-4 (cytotoxic T lymphocyte associated antigen 4) and PD-1L (Programmed Death 1 Ligand) play as immune system activation checkpoints that maintain immune tolerance and prevent autoimmunity These pathways are sometimes used by tumor cells to develop immune response evasion mechanisms, generating tolerance over these malignant cells and allowing their survival, favoring tumor progression [1,2,3]. SScchheemmeeooffiimmmmuunnee rreessppoonnssee eevvaassiioonn wwiitthh ssppeecciiaall iinntteerreesstt iinn CCTTLLAA--44 aanndd PPDD11--LL rroollee In relation to her cancer disease, during previous years she received surgical treatment (left hepatectomy and segment VII nodulectomy) and medical. A control MRI was performed at 4 months, observing persistence of the pituitary stalk thickening without significant changes

Discussion

Conclusions