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. 2021 Jun 7;9:678127. doi: 10.3389/fcell.2021.678127

TABLE 1.

B cell and TLS presence and abundance as prognostic factors in different tumors.

Author, year Tumor type N Sample type Method of assessment Finding

B lymphocytes
Ladanyi et al. (2011) Cutaneous melanoma 106 FFPE Immunohistochemistry High number of CD20+ B cells (intratumoral and peritumoral) associated with improved OS
Mahmoud et al. (2012) Breast cancer 1,470 FFPE Immunohistochemistry Higher total CD20+ B cell counts associated with better DFI and BCSS
Woo et al. (2014) Prostate carcinoma 53 FFPE Immunohistochemistry Intratumoral CD20+ B cells associated with cancer recurrence and progression
Germain et al. (2014) Lung cancer 74 early stage
122 advanced stage
FFPE Immunohistochemistry High density of follicular CD20+ B cells within TLSs associated with better OS
Castino et al. (2016) Pancreatic cancer 104 FFPE Immunohistochemistry High density of B cells within TLSs associated with improved DSS.
Miligy et al. (2017) Breast DCIS 36 FFPE Immunohistochemistry High number of CD20+ B cells associated with shorter RFI
Sakimura et al. (2017) Gastric cancer 226 FFPE Immunohistochemistry High number of CD20+ B cells associated with longer OS
Arias-Pulido et al. (2018) Inflammatory breast cancer 221 FFPE Immunohistochemistry CD20+PD-L1+ lymphocytes were an independent favorable prognostic factor for DFS and BCSS
Edin et al. (2019) Colorectal 316 FFPE Multiplexed immunohistochemistry and multispectral imaging High number of CD20+ B cells associated with improved DSS
Murakami et al. (2019) Gastric cancer 59 FFPE Double staining immunohistochemistry (CD19 and IL-10) Regulatory B cells (CD19+IL10+) associated with worse 5-year OS rate
Chen et al. (2020) NK/T-cell lymphoma 56 FFPE Immunohistochemistry High density of CD20+ B cells associated with improved OS
Petitprez et al. (2020) Sarcoma 496 STS public datasets (TCGA SARC,
GSE21050, GSE21122 and GSE30929)
Gene expression (TME deconvolution) B cell signature associated with improved OS

TLS

Coppola et al. (2011) Colorectal cancer 21 Fresh tumor Microarray Higher expression of a 12-chemokine TLS signature in long-term survivors
Vayrynen et al. (2014) Colorectal cancer 418 (cohort 1) FFPE H&E Higher TLS density (the number of follicles/the length of the invasive front) associated with improved 5-year survival
Hiraoka et al. (2015) Pancreatic cancer 308 FFPE Immunohistochemistry Higher relative area of intratumoral TLSs associated with improved OS and DFS
Schweiger et al. (2016) Colorectal cancer (lung metastases) 57 FFPE Immunohistochemistry The presence of TLSs was not associated with improved RFS or OS
Lee H.J. et al. (2016) Resected triple negative breast cancer 769 FFPE H&E Moderate or abundant TLSs associated with better DFS
Liu X. et al., 2017 Invasive breast cancer 248 FFPE Immunohistochemistry Presence of TLS associated with improved DFS in HER2+ tumors
Silina et al. (2018) Resected squamous cell lung carcinoma 138 FFPE H&E Number of TLSs per mm2 was the strongest prognostic factor
Calderaro et al. (2019) Resected hepatocellular carcinoma 273 FFPE H&E Presence of intratumoral TLSs associated with lower risk of early tumor relapse following surgery
Sofopoulos et al. (2019) Ductal breast carcinoma 112 FFPE H&E Patients with peritumoral TLSs had worse DFS and OS
Cabrita et al. (2020) Cutaneous melanoma 117 FFPE Immunohistochemistry Presence of TLSs and tumor associated CD8+ cells associated with improved OS
Li et al. (2020) Resected oral cancer 65 FFPE H&E Patients whose tumors were enriched for intratumoral TLSs had better DFS and OS
Tang et al. (2020) Lung cancer 133 FFPE Immunohistochemistry High TLS number per mm2 and relative area associated with improved 10-year survival
Rakaee et al. (2021) Lung cancer 553 FFPE Immunohistochemistry TLS score was an independent positive prognostic factor of DFS and OS, regardless of the quantification strategy used (four-scale semi-quantitative; absolute count of total TLSs; absolute count of total TLSs with germinal center)

TLS, tertiary lymphoid structures; FFPE, formalin-fixed paraffin-embedded samples; DFI, disease-free interval; BCSS, breast cancer specific survival; RFI, relapse-free interval; DCIS, ductal carcinoma in situ; DSS, disease-specific survival; OS, overall survival; STS, soft tissue sarcoma; RFS, recurrence-free survival; H&E, hematoxylin and eosin staining.