Thus, it may be possible to generate more potent, sustained T-cell responses in the tumor environment by promoting the in?ltration of tumor-reactive B cells. classical B cell markers CD19 and CD20. Although the marker expression may be influenced by the culture, one may still speculate on tumor-infiltrating B cells falsely counted as DCs – at least when CD83 was used as DC marker. Multi-color stainings on cryosections will help to clarify this question. Similarly, Nielsen et al shed Rabbit polyclonal to CD20.CD20 is a leukocyte surface antigen consisting of four transmembrane regions and cytoplasmic N- and C-termini. The cytoplasmic domain of CD20 contains multiple phosphorylation sites,leading to additional isoforms. CD20 is expressed primarily on B cells but has also been detected onboth normal and neoplastic T cells (2). CD20 functions as a calcium-permeable cation channel, andit is known to accelerate the G0 to G1 progression induced by IGF-1 (3). CD20 is activated by theIGF-1 receptor via the alpha subunits of the heterotrimeric G proteins (4). Activation of CD20significantly increases DNA synthesis and is thought to involve basic helix-loop-helix leucinezipper transcription factors (5,6) light into another open question: which functional subtypes of B cells infiltrate tumor tissues? To definitely answer this, our above mentioned cloning strategy will, together with classical analyses of different surface markers by immunohistochemical staining, possibly be very helpful. Impact on future diagnostic procedures and prognosis The contribution of B cells present in tumor tissues on the outcome of the disease is still largely cryptic. The data of Nielsen et al clearly support a positive prognostic value of CD20+ TIL in ovarian cancer. Together with recent similar findings of other groups on head and neck cancer, cutaneous melanoma and breast cancer, it is likely that the presence of CD20+ TIL may be a good prognosticator in general. Moreover, all the above mentioned analyses clearly focus on the B cell marker CD20 and broader analyses using B cell subset markers are definitely warranted in order to allow for diagnostic ideals of B cell subtypes infiltrating different cancers. Contrary to these findings, it has been demonstrated that B cells presence in tumor draining lymph nodes is definitely associated with lymphangiogenesis inside a mouse model, which subsequently increases metastasis. In human tumor, a metastasis-promoting part is definitely discussed for B1 lymphocytes in melanoma and B cell-secreted lymphotoxin can promote castration-resistant prostate malignancy. Taken collectively, these findings clearly imply that B lymphocytes subtypes and most likely additional tissue context parameters will become predictive for either antitumoral or tumor-promoting activity of tumor-infiltrating B cells. Impact on long term therapeutic concepts In my opinion, probably the most interesting discussion brought ahead by Nielsen et al is the following: during long term immune reactions as observed in autoimmunity, allograft rejection as well as chronic illness, B cells and T cells form so-called tertiary lymphoid constructions. Therefore, both cell types preserve a strong immune response in cooperative relationships in the affected site. The authors suggest that long term antitumoral immunotherapies should be designed as to mimic these Vitamin K1 chronic immune reactions: T-cell reactions are sustained over many weeks or years by direct relationships with co-localized B cells. Therefore, it may be possible to generate more potent, sustained T-cell reactions in the tumor environment by advertising the in?ltration of tumor-reactive B cells. This line of argumentation is definitely well taken, since in some colorectal cancers tumor-infiltrating B cells typically reside in tertiary lymphoid constructions together with additional tumor-infiltrating leukocyte populations therefore permitting anti-tumor effects. This so-called Crohns like reaction has repeatedly been associated with very good prognosis for colorectal malignancy and is especially associated with the molecular subtype with best prognostic behaviour; i.e., microsatellite-instability. Another very promising strategy may foundation on the above mentioned Vitamin K1 unique potential of B cells to specifically concentrate Vitamin K1 antigens their membrane-bound Ig molecules. I would like to speculate that tumor-antigen-specific B cells will have an enormous T cell stimulatory potential. Thus, cellular therapies can be envisioned basing on isolation and development of tumor-infiltrating and antigen-specific B cells. In summary, improved understanding of the practical phenotype of tumor-infiltrating B cells (CD20+ but probably also CD20neg B cells), their target antigens, and their mechanism of recruitment to target tissues may not only help to understand the part of B cells in the natural curse of tumor diseases but also will have potentially strong impact on individuals diagnosis and finally will facilitate the design of more effective immunotherapies for the treatment of tumor. Footnotes P- Reviewer Glassy MC S- Editor Gou SX L-.
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