In December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus causing Coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, and has since infected more than 750 million people around the globe [1], [2]. Severe SARS-CoV-2 infections are associated with immune dysregulation involving reduced production of type I and type III interferons and hypersecretion of pro-inflammatory cytokines such as IL-6, IFN- γ, TNFα [3], [4], [5]. Consequently, these elevated levels of cytokines have a detrimental effect on T cell survival and proliferation [6]. Activated macrophages, neutrophils, and monocytes release additional pro-inflammatory cytokines in response to the depletion of lymphocytes, amplifying the production of a cytokine storm. This contributes to the rapid progression of patients to severe conditions such as acute respiratory distress syndrome and multiple organ dysfunction.

The pandemic poses a significant challenge for patients with an immunocompromised status due to their higher risk of developing severe infections than the general population. Cancer patients are particularly vulnerable as they are susceptible to disease-associated and therapy-induced dysregulation of the immune system, and severe infection places these patients at an elevated risk of morbidity and mortality. The upregulation of cytokines such as IL-1β, IL-6, TNF, IL-8, and IL-17 is associated with advanced stages of malignancy [7]. Moreover, overexpression of vascular endothelial growth factor in patients with solid tumors impairs the development and function of immune cells in the microenvironment [8]. When these cytokines are upregulated in the context of severe SARS-CoV-2 infection, it may contribute to the poorer outcomes observed in some cancer patients. Beyond the direct health effects, the pandemic has increased cancer-specific mortality as medical procedures have been modified, delayed, or canceled [9].

Four years after the pandemic outbreak, remarkable efforts have been dedicated to understating the challenges posed by the SARS-CoV-2 virus and its variants of concern (VOC) in patients with cancer [10]. Multiple vaccine types have been developed and implemented, mainly using the viral spike (S) protein, demonstrating remarkable effectiveness in preventing infection and symptomatic illness [11], [12]. One unique feature of these vaccines is their ability to stimulate both humoral and cellular immunity, crucial in providing enduring protection against the virus. However, while COVID-19 vaccines have provided some protection against infection and severe illness in individuals with cancer, there have been noticeable reductions in their ability to trigger an immune response and their effectiveness in real-world scenarios [2], [13], [14]. The suboptimal immunogenicity and the decline in immunity after vaccination have highlighted the necessity for booster vaccinations, particularly among this susceptible group. Analyzing and comprehending how the immune system responds to different vaccination regimens for SARS-CoV-2 and VOCs among cancer patients is crucial for shaping clinical and public health strategies.

In this review, we provide an updated overview of the efficacy of COVID-19 vaccines in cancer patients, as well as those undergoing hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor (CAR) T cell therapy, by exploring the extent of the humoral and cellular immune response to COVID-19 vaccination. Furthermore, we describe risk factors and potential biomarkers for severe SARS-CoV-2 infection and vaccine responses and offer suggestions to increase SARS-CoV-2 protection in cancer patients.