B cells and the Boob

B

If you rememeber one of the potential side effects of cladribine was thought to be cancer. We looked at this and the occurrance of cancer was not really more than the effect of life. Two years in a trial is rather short to assess the cancr risk.This will show itself with time. However removing large parts of your immune system is going to increase the risk..Never the less, this European-derived treatment got held up by the FDA, resulting in a 6 years delay in approval. It turned out there were only three cancers verses none in the placebo in the trial.

Ocrelizumab generated in the USA came along and sailed past the FDA with 9 cancers verses 0. (Not alot of consistency, but there were larger trial-results available). Importantly there appeared to be more breast cancers.

ProfG suggested this may be a fluke but was taken to task, by the suggestion that B cells are involved in cancer immunity and accumulate in breast tissue. This paper puts more meat on this bone.

Tumor infiltrating B-cells signal functional humoral immune responses in breast cancer. Garaud S, Buisseret L, Solinas C, Gu-Trantien C, de Wind A, Van den Eynden G, Naveaux C, Lodewyckx JN, Boisson A, Duvillier H, Craciun L, Ameye L, Veys I, Paesmans M, Larsimont D, Piccart-Gebhart M, Willard-Gallo K.JCI Insight. 2019 Aug 13;5. pii: 129641. 

Tumor-infiltrating B-cells (TIL-B) in breast cancer (BC) have previously been associated with improved clinical outcomes; however, their role(s) in tumor immunity is not currently well known. This study confirms and extends the correlation between higher TIL-B densities and positive outcomes through an analysis of HER2 (a marker on cancer cells) -positive and triple-negative BC patients from the BIG 02-98 clinical trial (10yr mean follow-up). Fresh tissue analyses identify an increase in TIL-B density in untreated primary BC compared to normal breast tissues, which is associated with global, CD4+ and CD8+ TIL, higher tumor grades, higher proliferation and hormone receptor negativity. All B-cell differentiation stages are detectable but significant increases in memory TIL-B are consistently present. BC with higher infiltrates are specifically characterized by germinal center TIL-B, which in turn are correlated with TFH TIL and antibody-secreting TIL-B principally located in tertiary lymphoid structures. Some TIL-B also interact directly with tumor cells. Functional analyses reveal TIL-B are responsive to BCR stimulation ex vivo, express activation markers and produce cytokines and immunoglobulins despite reduced expression of the antigen-presenting molecules HLA-DR and CD40. Overall, these data support the concept that ongoing humoral immune responses are generated by TIL-B and help to generate effective anti-tumor immunity at the tumor site.

So maybe B cells are important in tumour immunity, so if you are taking ocrelizumab, rituximab or any B cell depleter…which is all of them, ensure you regularly check you Boobs and Moobs and report anything out of the norm.

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