B cells and tertiary lymphoid structures promote immunotherapy response Journal Article
| Authors: | Helmink, B. A.; Reddy, S. M.; Gao, J.; Zhang, S.; Basar, R.; Thakur, R.; Yizhak, K.; Sade-Feldman, M.; Blando, J.; Han, G.; Gopalakrishnan, V.; Xi, Y.; Zhao, H.; Amaria, R. N.; Tawbi, H. A.; Cogdill, A. P.; Liu, W.; LeBleu, V. S.; Kugeratski, F. G.; Patel, S.; Davies, M. A.; Hwu, P.; Lee, J. E.; Gershenwald, J. E.; Lucci, A.; Arora, R.; Woodman, S.; Keung, E. Z.; Gaudreau, P. O.; Reuben, A.; Spencer, C. N.; Burton, E. M.; Haydu, L. E.; Lazar, A. J.; Zapassodi, R.; Hudgens, C. W.; Ledesma, D. A.; Ong, S. F.; Bailey, M.; Warren, S.; Rao, D.; Krijgsman, O.; Rozeman, E. A.; Peeper, D.; Blank, C. U.; Schumacher, T. N.; Butterfield, L. H.; Zelazowska, M. A.; McBride, K. M.; Kalluri, R.; Allison, J.; Petitprez, F.; Fridman, W. H.; Sautès-Fridman, C.; Hacohen, N.; Rezvani, K.; Sharma, P.; Tetzlaff, M. T.; Wang, L.; Wargo, J. A. |
| Article Title: | B cells and tertiary lymphoid structures promote immunotherapy response |
| Abstract: | Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1–10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11–15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | immunohistochemistry; signal transduction; treatment response; drug tolerability; cancer recurrence; bevacizumab; cancer risk; drug safety; cancer staging; flow cytometry; phenotype; electron microscopy; ipilimumab; cancer immunotherapy; melanoma; immune system; gene expression; gene expression profiling; renal cell carcinoma; b lymphocyte; cancer inhibition; immune response; algorithm; microarray analysis; cellular distribution; open study; immunity; tumor; cytotoxic t lymphocyte antigen 4; memory cell; cell expansion; immunocompetent cell; rna extraction; programmed death 1 receptor; hybridization; conjugation; cell; chemokine receptor cxcr4; exosome; b lymphocyte receptor; cancer prognosis; dabrafenib; trametinib; nivolumab; limit of quantitation; cancer; human; priority journal; article; tertiary lymphoid structure; mass cytometry; receptor type tyrosine protein phosphatase c; microenvironment cell population counter algorithm; single cell rna seq |
| Journal Title: | Nature |
| Volume: | 577 |
| Issue: | 7791 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-01-23 |
| Start Page: | 549 |
| End Page: | 555 |
| Language: | English |
| DOI: | 10.1038/s41586-019-1922-8 |
| PUBMED: | 31942075 |
| PROVIDER: | scopus |
| PMCID: | PMC8762581 |
| DOI/URL: | |
| Notes: | Article -- Roberta Zappasodi's name is misspelled in the PDF as Zapassodi -- Export Date: 3 February 2020 -- Source: Scopus |
