In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-25)
Abstract:
Lymphoid neogenesis gives rise to tertiary lymphoid structures (TLS) in the periphery of multiple cancer types including muscle invasive bladder cancer (MIBC) where it has positive prognostic and predictive associations. Here, we explored molecular, clinical, and histological data of The Cancer Genome Atlas, as well as the IMvigor210 dataset to study factors associated with TLS development and function in the tumor microenvironment (TME) of MIBC. We also analyzed tumor immune composition including TLS in an independent, retrospective MIBC cohort. We found that the combination of TLS density and tumor mutational burden provides a novel independent prognostic biomarker in MIBC. Gene expression profiles obtained from intratumoral regions that rarely contain TLS in MIBC showed poor correlation with the prognostic TLS density measured in tumor periphery. Tumors with high TLS density showed increased gene signatures as well as infiltration of activated lymphocytes. Intratumoral B-cell and CD8 + T-cell co-infiltration was frequent in TLS-high samples, and such regions harbored the highest proportion of PD-1 + TCF1 + progenitor-like T cells, naïve T cells, and activated B cells when compared to regions predominantly infiltrated by either B cells or CD8 + T cells alone. We found four TLS maturation subtypes; however, differences in TLS composition appeared to be dictated by the TME and not by the TLS maturation status. Finally, we identified one downregulated and three upregulated non-immune cell-related genes in TME with high TLS density, which may represent candidates for tumor-intrinsic regulation of lymphoid neogenesis. Our study provides novel insights into TLS-associated gene expression and immune contexture of MIBC and indicates towards the relevance of B-cell and CD8 + T-cell interactions in anti-tumor immunity within and outside TLS.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.793992
DOI:
10.3389/fimmu.2021.793992.s001
DOI:
10.3389/fimmu.2021.793992.s010
DOI:
10.3389/fimmu.2021.793992.s002
DOI:
10.3389/fimmu.2021.793992.s011
DOI:
10.3389/fimmu.2021.793992.s012
DOI:
10.3389/fimmu.2021.793992.s013
DOI:
10.3389/fimmu.2021.793992.s014
DOI:
10.3389/fimmu.2021.793992.s003
DOI:
10.3389/fimmu.2021.793992.s004
DOI:
10.3389/fimmu.2021.793992.s005
DOI:
10.3389/fimmu.2021.793992.s006
DOI:
10.3389/fimmu.2021.793992.s007
DOI:
10.3389/fimmu.2021.793992.s008
DOI:
10.3389/fimmu.2021.793992.s009
DOI:
10.3389/fimmu.2021.793992.s015
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8