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Immune-checkpoint inhibitors from cancer to COVID?19: A promising avenue for the treatment of patients with COVID?19 (Review).

ABSTRACT: The severe acute respiratory syndrome associated coronavirus?2 (SARS?CoV?2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID?19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off?label for the treatment of COVID?19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune?checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death?1 (PD?1)/PD ligand-1 (PD?L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID?19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T?cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti?tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T?cell exhaustion, which is also observed following SARS?CoV?2 infection. Importantly, when treated with anti?PD?1 and anti?PD?L1 antibodies, they restore their T?cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti?PD?1 antibody administration to both cancer and non?cancer individuals affected by COVID?19. The results may prove the hypothesis that restoring exhausted T?cells may be a winning strategy to beat SARS?CoV?2 infection.

SUBMITTER: Vivarelli S

PROVIDER: S-EPMC7864014 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Immune-checkpoint inhibitors from cancer to COVID‑19: A promising avenue for the treatment of patients with COVID‑19 (Review).

Vivarelli Silvia S Falzone Luca L Torino Francesco F Scandurra Giuseppa G Russo Giulia G Bordonaro Roberto R Pappalardo Francesco F Spandidos Demetrios A DA Raciti Giuseppina G Libra Massimo M

International journal of oncology 20201214 2

The severe acute respiratory syndrome associated coronavirus‑2 (SARS‑CoV‑2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID‑19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, inc ...[more]

PMID: 33491759

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Project description:Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient's own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.

Dataset Information

Immune-checkpoint inhibitors from cancer to COVID?19: A promising avenue for the treatment of patients with COVID?19 (Review).

Publications

Immune-checkpoint inhibitors from cancer to COVID‑19: A promising avenue for the treatment of patients with COVID‑19 (Review).

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