The (1→6)-β-Glucan Moiety Represents a Cross-Reactive Epitope of Infection-Induced Malignancy Surveillance

Abstract

Exposure to pathogen-associated molecular patterns (PAMPs) by vaccination or infection is known to have beneficial effects on neoplastic diseases, although the underlying molecular mechanisms are so far unclear. In this article, we report that Abs against (1→6)-β-d-glucan, a typical microbial PAMP and a major target for high titer circulating natural Abs in healthy human subjects, cross-recognize a novel tumor-associated carbohydrate Ag on cancer cells. The (1→6)-β-glucan cross-reactive moiety is immunologically dominant in tumor cells, as C57BL/6 mice harboring EL-4 solid tumors produced anti-(1→6)-β-glucan Abs and the titer of which significantly correlated with enhanced survival and smaller tumor burden. Moreover, the (1→6)-β-glucan–specific Abs exhibited potent tumoricidal activities in vitro. C57BL/6 mice immunized with Candida albicans produced protective immunity against inoculated EL-4 tumors, which was attributed to the formation of (1→6)-β-glucan–specific Abs. Importantly, (1→6)-β-glucan–specific Abs significantly prolonged the survival and reduced the tumor size in mice inoculated with EL-4 tumors. Our results demonstrate that the (1→6)-β-glucan cross-reactive moiety represents a focal point between infection immunity and cancer surveillance, and natural Abs against this epitope may contribute to the first-line antitumor surveillance in humans. Our data also provide important explanation for the long-observed relationship between feverish infection and concurrent remission from cancer.

Development of a novel β-1,6-glucan–specific detection system using functionally-modified recombinant endo-β-1,6-glucanase

“…In this study, we developed a ␤-1,6-glucan detection system with an animal-free recombinant protein. Before focusing on ␤-1,6-glucanase, we had considered other candidates for a ␤-1,6-glucan probe, such as the Musa acuminata-derived lectin (29), yeast-derived K1/K2 killer toxins (30), and a mAb (31). However, we excluded these candidates for the following reasons: the lectin has insufficient structure specificity; killer toxins are structurally unstable; and a mAb requires high cost for sufficient production in high-quality grade.…”

Functional immune boosters; the herb or its dead microbiome? Antigenic TLR4 agonist MAMPs found in 65 medicinal roots and algae’s

“…While the plant microbiome has been extensively studied in relation to its growth, health, maturation, influence on environmental ecology ( Berihu et al, 2023 ; Cook et al, 2023 ; Yin et al, 2023 ; Zhou et al, 2022 ) and food safety ( Kazi et al, 2018 ; Wassermann et al, 2022 ), very little is known about the characterization or concentration of bioactive remnants of microbial debris in edible foods, including pathogenic after being intentionally destroyed. Specifically, there is limited knowledge about foods which would as a design by mother nature, contain high concentration of microbial/pathogen associated molecular patterns (MAMPs/PAMPS) with known capacity to modulate the immune system, this the fundamental basis for the development of vaccines, adjuvants and immunotherapies ( Dong et al, 2014 ; Dubey et al, 2014 ; Nelson, 2022 ; Roeder et al, 2004 ; Rossi and Mastroeni, 2022 ; Zelechowska et al, 2022 ). Immune provocation is based on the ability to distinguish self from non-self, accomplished by host pattern recognition receptors (PRRs) that recognize foreign MAMPS (non-self) and include among others – the lipid A subregion of bacterial lipopolysaccharide (LPS) from gram negative rods.…”

Carbohydrate-Mimetic Peptides for Pan Anti-Tumor Responses

“…Consequently, certain carbohydrate forms profoundly affect both the pathophysiology of infection and neoplasia (Table 1). A unique advantage in targeting tumor-associated carbohydrate antigens (TACAs) is that multiple proteins and lipids on cancer cells can be modified with the same carbohydrate structure which might be shared with bacterial antigens (2). Thus, targeting TACAs has the potential to broaden the spectrum of antigens recognized by the immune response, thereby lowering the risk of developing resistant tumors due to the loss of a given protein antigen.…”