Potential protective role of the anti-PD-1 blockade against SARS-CoV-2 infection

Abstract

The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019, and its global dissemination became the coronavirus disease 2019 (COVID-19) pandemic declared by the World Health Organization (WHO) on 11 March 2020. In patients undergoing immunotherapy, the effect and path of viral infection remain uncertain. In addition, viral-infected mice and humans show T-cell exhaustion, which is identified after infection with SARS-CoV-2. Notably, they regain their T-cell competence and effectively prevent viral infection when treated with anti-PD-1 antibodies. Four clinical trials are officially open to evaluate anti-PD-1 antibody administration's effectiveness for cancer and non-cancer individuals influenced by COVID-19 based on these findings. The findings may demonstrate the hypothesis that a winning strategy to combat SARS-CoV-2 infection could be the restoration of exhausted T-cells. In this review, we outline the potential protective function of the anti-PD-1 blockade against SARS-CoV-2 infection with the aim to develop SARS-CoV-2 therapy.

Keywords: Anti-PD-1; COVID-19; Immunotherapy; SARS-CoV-2; T-cells.

Graphical abstract

Fig. 1

PD-1 Blocking Antibodies. In patients with severe pneumonia caused by COVID-19, monoclonal antibodies that block PD-1 activity will increase T cell proliferation, cytokine production and reduce death.

Fig. 2

Blockade of PD-1 or CTLA-4 signaling in tumor immunotherapy. T cells use their T-cell receptor (TCR) to detect antigens provided by the MHC on cancer cells' surfaces. This first signal is insufficient to activate T cells; therefore, the B7 costimulatory molecules B7–1 (or CD80) and B7–2 (or CD86) must send a second signal. CTLA-4 (cytotoxic T-lymphocyte–associated antigen 4) is upregulated shortly after T-cell activation and initiates negative control signaling on T cells throughout ligation with antigen-presenting cells' B7 costimulatory molecules. These molecules have activation signals when they bind to CD28 and inhibitory signals when they bind to CTLA-4. CTLA-4 interacts with costimulatory molecules mainly during the priming process of a T-cell response within lymph nodes. T cells release the programmed death 1 (PD-1) inhibitory receptor during long-term antigen exposure, and ligation with PD-L1 and PD-L2, which are mainly expressed in inflamed tissues and the tumor microenvironment, results in the negative control of T cells. In peripheral tissues, the PD-1 association occurs during the effector process of a T-cell response. When antibodies to PD-1 or PD-L1 are used to inhibit it, T cells with cancer specificity are preferentially activated .

Fig. 3

Using the innate effector lymphocyte natural killer (NK) cell, potential immunotherapeutic techniques for cancer treatment have been identified. 6 major strategies are highlighted to increase the effector activity of NK cells and assist in the targeting of cancer cells. Some are clinically licensed, such as cytokines and immune checkpoint inhibitors, whereas others are still in the pre-clinical stage. To improve the effectiveness of these therapies in solid tumors, further research is required .

Fig. 4

A strategy for producing personalized viral-specific T cells as a possible therapeutic for preventing and/or treating SARS-CoV-2 infections in susceptible communities, including cancer patients. SARS-CoV-2 peptides are pulsed into an individual's monocytic-DCs and are then used to prime the same individual's T cells, resulting in SARS-CoV-2-specific T cells. These T cells may be cryopreserved or infused into the vulnerable individual as prevention or treatment against COVID-19 , , .