BCR and TCR repertoires in the NeoALTTO and CALGB 40601 trials
tumor
TUMOR, HER2-POSITIVE BREAST CANCER
Aiming at investigating the complexity of the immune response in HER2-positive breast cancer, we explored the diversity of BCR and TCR repertoires in pre-treatment baseline tumor samples. The MiXCR toolIn NeoALTTO, all samples had at least one read mapping to BCR, while one sample did not have any read mapping to TCR. In the CALGB 40601 study, all samples showed reads mapping to both BCR and TCR. As the library size can impact the number of BCR/TCR reads, for the subsequent analyses we normalized the number of BCR/TCR reads by the total number of reads mapping to genes in each sample. The number of reads mapping to TCR was significantly lower than BCR in both studies, and the number of normalized reads and clones were significantly higher in NeoALTTO compared to CALGB 40601 (Supplementary data The proportions of reads mapping to the different immunoglobulin and TCR chains are shown in Supplementary Fig. From here on, we refer to BCR/TCR repertoire characteristics as the global metrics calculated on all reads mapping to chains forming either the BCR or TCR, with clones defined separately for each chain as detailed in the METHODS, representing the whole clonal repertoire.The correlation among different BCR/TCR measures is also shown in Supplementary Figs. Isotypes (IgG, IgA, IgM, IgD, IgE) from BCR heavy chains were also computed (details in METHODS). In both studies, the majority of the BCR heavy chain reads were from IgG, followed by IgA and IgM (Supplementary Fig 