Clinically Relevant Immune Responses against Cytomegalovirus: Implications for Precision Medicine.

Joana R Lérias,Carolina Condeço,Nuno Figueiredo,João Martins,Carlos Carvalho,Georgia Paraschoudi,Martin Rao,Ernest Dodoo,Eric De Sousa,Markus Maeurer,Inês Silva,Elke Jäger

doi:10.3390/ijms20081986

Abstract

Immune responses to human cytomegalovirus (CMV) can be used to assess immune fitness in an individual. Further to its clinical significance in posttransplantation settings, emerging clinical and translational studies provide examples of immune correlates of protection pertaining to anti-CMV immune responses in the context of cancer or infectious diseases, e.g., tuberculosis. In this viewpoint, we provide a brief overview about CMV-directed immune reactivity and immune fitness in a clinical context and incorporate some of our own findings obtained from peripheral blood or tumour-infiltrating lymphocytes (TIL) from patients with advanced cancer. Observations in patients with solid cancers whose lesions contain both CMV and tumour antigen-specific T-cell subsets are highlighted, due to a possible CMV-associated “bystander” effect in amplifying local inflammation and subsequent tumour rejection. The role of tumour-associated antibodies recognising diverse CMV-derived epitopes is also discussed in light of anti-cancer immune responses. We discuss here the use of anti-CMV immune responses as a theranostic tool—combining immunodiagnostics with a personalised therapeutic potential—to improve treatment outcomes in oncological indications.

Highlights

Intact immune responses to cytomegalovirus (CMV) in humans are generally acknowledged as a marker of immunological fitness [1]
We provide a brief overview about CMV-directed immune reactivity and immune fitness in a clinical context and incorporate some of our own findings obtained from peripheral blood or tumour-infiltrating lymphocytes (TIL) from patients with advanced cancer
The role of tumour-associated antibodies recognising diverse CMV-derived epitopes is discussed in light of anti-cancer immune responses

Summary

Introduction

Intact immune responses to cytomegalovirus (CMV) in humans are generally acknowledged as a marker of immunological fitness [1]. Herpesviruses, including CMV and EBV, are known to establish latency in humans, the effect of which leads to unique and clinically relevant immunomodulation which—based on clinical and preclinical studies—stretches across the spectrum of immune-associated diseases to protective cellular immune responses in healthy individuals [6]. The phenomenon of inducing and maintaining a general state of systemic inflammation marked by upregulated levels of pro-inflammatory cytokines (i.e., IL-18, IL-6, IP-10, TNF-α, and IFN-γ) in serum during latency after a primary infection is a characteristic of CMV, as shown in the context of renal transplant recipients [14] and in CMV-positive, healthy humans [15,16]. CMV-driven inflammation—if not overt—maybe beneficial in potentiating general immune surveillance and control in the host, such as in cancer [17] and drug-susceptible pulmonary tuberculosis [18]

CMV–Host Interactions in Cancer

TIL from BCC tissue

Harnessing Anti-CMV Immunomodulation for Precision Oncology

Findings

Conclusions