Antitumor mAb bind to tumors and activate complement, coating tumors with iC3b. Intravenously administered yeast β-1,3;1,6-glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b) receptors (CR3; CD11b/CD18) of circulating granulocytes, enabling CR3 to trigger cytotoxicity of iC3b-coated tumors. Recent data indicated that barley β-1,3;1,4-glucan given orally similarly potentiated the activity of antitumor mAb, leading to enhanced tumor regression and survival. This investigation showed that orally administered yeast β-1,3;1,6-glucan functioned similarly to barley β-1,3;1,4-glucan with antitumor mAb. With both oral β-1,3-glucans, a requirement for iC3b on tumors and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in mice deficient in C3 or CR3. Barley and yeast β-1,3-glucan were labeled with fluorescein to track their oral uptake and processing in vivo. Orally administered β-1,3-glucans were taken up by macrophages that transported them to spleen, lymph nodes, and bone marrow. Within the bone marrow, the macrophages degraded the large β-1,3-glucans into smaller soluble β-1,3-glucan fragments that were taken up by the CR3 of marginated granulocytes. These granulocytes with CR3-bound β-1,3-glucan-fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to a site of complement activation resembling a tumor coated with mAb.

Intravenous and orally administered β-glucans promote tumor regression and survival by priming granulocyte and macrophage C receptor 3 (CR3, iC3bR and CD11b/CD18) to trigger the cytotoxicity of tumor cells opsonized with iC3b via anti-tumor Abs. Despite evidence for priming of macrophage CR3 by oral β-glucan in vivo, the current study in C57BL/6 and BALB/c mice showed that granulocytes were the essential killer cells in mAb- and oral β-glucan-mediated tumor regression, because responses were absent in granulocyte-depleted mice. Among granulocytes, neutrophils were the major effector cells, because tumor regression did not occur when C5a-dependent chemotaxis was blocked with a C5aR antagonist, whereas tumor regression was normal in C3aR−/− mice. Neutrophil recruitment by C5a in vivo required amplification via leukotriene B4, because both C5a-mediated leukocyte recruitment into the peritoneal cavity and tumor regression were suppressed in leukotriene B4R-deficient (BLT-1−/−) mice.

Colorectal cancer (CRC) remains one of the most common malignancies diagnosed worldwide. The pathogenesis of CRC is complex and involves, among others, accumulation of genetic predispositions and epigenetic factors, dietary habits, alterations in gut microbiota, and lack of physical activity. A growing body of evidence suggests that immune cells play different roles in CRC, comprising both pro-and anti-tumorigenic functions. Immunosuppression observed during cancer development and progression is a result of the orchestration of many cell types, including myeloid-derived suppressor cells (MDSCs). MDSCs, along with other cells, stimulate tumor growth, angiogenesis, and formation of metastases. This article focuses on MDSCs in relation to their role in the initiation and progression of CRC. Possible forms of immunotherapies targeting MDSCs in CRC are also discussed.

The SARS-CoV-2 infection [coronavirus disease 2019 (COVID-19)] is associated with severe lymphopenia and impaired immune response, including expansion of myeloid cells with regulatory functions, e.g., so-called low-density neutrophils, containing granulocytic myeloid-derived suppressor cells (LDNs/PMN-MDSCs). These cells have been described in both infections and cancer and are known for their immunosuppressive activity. In the case of COVID-19, long-term complications have been frequently observed (long-COVID). In this context, we aimed to investigate the immune response of COVID-19 convalescents after a mild or asymptomatic course of disease. We enrolled 13 convalescents who underwent a mild or asymptomatic infection with SARS-CoV-2, confirmed by a positive result of the PCR test, and 13 healthy donors without SARS-CoV-2 infection in the past. Whole blood was used for T-cell subpopulation and LDNs/PMN-MDSCs analysis. LDNs/PMN-MDSCs and normal density neutrophils (NDNs) were sorted out by FACS and used for T-cell proliferation assay with autologous T cells activated with anti-CD3 mAb. Serum samples were used for the detection of anti-SARS-CoV-2 neutralizing IgG and GM-CSF concentration. Our results showed that in convalescents, even 3 months after infection, an elevated level of LDNs/PMN-MDSCs is still maintained in the blood, which correlates negatively with the level of CD8+ and double-negative T cells. Moreover, LDNs/PMN-MDSCs and NDNs showed a tendency for affecting the production of anti-SARS-CoV-2 S1 neutralizing antibodies. Surprisingly, our data showed that in addition to LDNs/PMN-MDSCs, NDNs from convalescents also inhibit proliferation of autologous T cells. Additionally, in the convalescent sera, we detected significantly higher concentrations of GM-CSF, indicating the role of emergency granulopoiesis. We conclude that in mild or asymptomatic COVID-19 convalescents, the neutrophil dysfunction, including propagation of PD-L1-positive LDNs/PMN-MDSCs and NDNs, is responsible for long-term endotype of immunosuppression.

Prostate cancer (PC) is the second most often diagnosed malignancy in men and one of the major causes of cancer death worldwide. Despite genetic predispositions, environmental factors, including a high-fat diet, obesity, a sedentary lifestyle, infections of the prostate, and exposure to chemicals or ionizing radiation, play a crucial role in PC development. Moreover, due to a lack of, or insufficient T-cell infiltration and its immunosuppressive microenvironment, PC is frequently classified as a “cold” tumor. This is related to the absence of tumor-associated antigens, the lack of T-cell activation and their homing into the tumor bed, and the presence of immunological cells with regulatory functions, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg), and tumor-associated macrophages (TAMs). All of them, by a variety of means, hamper anti-tumor immune response in the tumor microenvironment (TME), stimulating tumor growth and the formation of metastases. Therefore, they emerge as potential anti-cancer therapy targets. This article is focused on the function and role of MDSCs in the initiation and progression of PC. Clinical trials directly targeting this cell population or affecting its biological functions, thus limiting its pro-tumorigenic activity, are also presented.