Table 1. Prognostic impact of B cells and TLS in human cancers.
| Cancer type | Number of cases | Result | Reference |
|---|---|---|---|
| Biliary tract cancer | 323 | CD20 and CD8 infiltration correlate with improved OS | Goeppert et al., 2013 |
| BC | 60 | The B cell–attracting chemokine CXCL13 correlates with PFS long-term survival | Gu-Trantien et al., 2017 |
| BC | 1,200 | CD20+ infiltration correlates with DSS and PFS | Mahmoud et al., 2012 |
| BC | 269 | CD38+ plasma cells infiltration correlates with better disease-free survival, but not OS | Yeong et al., 2018 |
| BC | 489 | Coexistence of B reg and T reg cells in TLS correlates with shorter metastasis-free survival | Ishigami et al., 2019 |
| BC | 728 | B cell signatures correlates with improved PFS | Iglesia et al, 2016 |
| ccRCC | 526 (TCGA); 28 | B cell lineage signature demonstrates no impact on survival; B cell signature correlates with response to ICIs | Helmink et al., 2020 |
| CRC | 107 | B (CD20) cell and T (CD8) cell infiltration and B cell–attracting CXCL13 chemokine correlate with longer PFS | Bindea et al., 2013 |
| CRC | 351 stage II and III | TLS density correlates with longer PFS in stage II, but not stage III, patients | Di Caro et al., 2014 |
| CRC | 557 | CD20, CD138, and IGKC infiltration correlate with improved OS | Berntsson et al., 2018 |
| CRC | 316 | High infiltration of CD20+ B cells correlates with improved DSS and slightly increases the prognostic effect of CD8+ T lymphocytes while having no prognostic effect on patients with tumors poorly infiltrated by CD8+ cytotoxic T lymphocytes | Edin et al., 2019 |
| Gastric cancer | 59 | IL-10+CD19+ cells are associated with shorter survival | Murakami et al., 2019 |
| Gastric cancer | 226 | Majority of B cells in gastric cancer are located in TLSs and associated with better OS | Yamakoshi et al., 2020 |
| Gastrointestinal stromal tumors | 111 | TLS density (H&E) correlates with longer OS and PFS | Lin et al., 2020 |
| HCC | 462 | TLS density (H&E) correlates with longer OS and PFS | Li et al., 2020a |
| HCC | 273 and 226 | Density of mature TLS (H&E) and TLS signature associated with lower risk of early recurrence | Calderaro et al., 2019 |
| HCC | 120 and 200 | CD20+ B cells located in the invasive margin colocalize and correlate with CD8, and a positive correlation is found between the density of B cells and OS or RFS; simultaneously, high densities of CD20+ and CD8+ cells are significantly associated with both prolonged OS and recurrence-free survival | Shi et al., 2013 |
| HCC | 112 | Density of tumor-infiltrating CD19+ B cells correlates with superior survival; CD20 and CD3 correlates with high intratumoral densities of both CD20+ B cells, and CD3+ T cells had longer survival compared with those with low densities of both subsets | Garnelo et al., 2017 |
| Head and neck cancer | 30 | Peritumoral B cell infiltration correlates with prolonged OS irrespective of IL-12 treatment | van Herpen et al., 2008 |
| Lung | 118 | Follicular CD20+ B cells and TLS density correlate with longer DSS | Germain et al., 2014 |
| Lung | 138 | TLSs are associated with good prognosis in untreated lung squamous cell carcinoma; corticosteroids may be detrimental to TLS formation | Siliņa et al., 2018 |
| Melanoma, primary cutaneous | 82 | Mature DC/T cell aggregate density correlates with favorable prognosis | Ladányi et al., 2007 |
| Melanoma | 25 | Frequency of plasmablast-like cells and naive B cells in pretherapy melanomas is higher in patients responding to ICB | Griss et al., 2019 |
| Melanoma | 164 | CD20 and CD8 infiltration correlates with improved survival; a CD20+ and CD8+ cell combination is the best prognosticator of survival; TLS gene signature predicts prognosis and response to ICI | Cabrita et al., 2020 |
| Melanoma | 136, 28, and 21 | B cell lineage signature demonstrates prolonged OS; CD20+, B cell signature, and TLS densities predict response to ICI | Helmink et al., 2020 |
| Melanoma, primary cutaneous | 98 | CD20 infiltration associated with longer OS | Garg et al., 2016 |
| Melanoma, primary cutaneous | 473 | Memory B cell score and increased clonality of the BCR repertoire are associated with longer OS; lack of an assembled BCR in pretreatment tumor tissues is associated with a lack of antitumor response to a CTLA-4 inhibitor; B reg cell score is associated with shorter OS and lack of response to CTLA4 | Selitsky et al., 2019 |
| Lung | 118 | Follicular CD20+ B cell and TLS density correlates with longer DSS | Germain et al., 2014 |
| Oral cancer | 65 | TLS density correlates with longer PFS and OS | Li et al., 2020b |
| Ovarian cancer | 172 | Tumor-infiltrating plasma cells are associated with TLSs, cytolytic response, and favorable prognosis | Kroeger et al., 2016 |
| Ovarian cancer | 194 | CD20+ infiltration improves the favorable impact of CD8+ T cells on DSS; tumors positive for both CD8 and CD20 TIL showed markedly greater DSS compared with those positive for CD8 TIL alone | Nielsen et al., 2012 |
| Ovarian cancer | 199 | CD20+ and CD8+ immune infiltrates and the combination correlate with improved DSS | Milne et al., 2009 |
| Ovarian cancer | 135 | CD20 infiltrate correlates with improved 5-yr and 10-yr survival | Santoiemma et al., 2016 |
| Ovarian cancer, omental metastases | 92 | B cells support the development of antitumor immune response | Montfort et al., 2017 |
| Pancreas | 534 | TLS density (H&E) correlate with longer DSS | Hiraoka et al., 2015 |
| Several tumor types | 3,485 | B and T cell signatures correlate with improved OS in BC (821), lung cancer (267), and melanoma (329); BCR diversity associated with OS in melanoma (329) and RCC (461) | Iglesia et al, 2016 |
| STS | 496 and 47 | B cell lineage signature associated with longer OS independently of T cell signature and PD1, PD-L1, and Foxp3 gene expression; TLS-rich group predicts PFS and response to ICIs independently of STS histology | Petitprez et al., 2020 |
| Urothelial urinary bladder cancer | 31 | CD20+ B cells in follicle-like structures correlate with longer survival; B reg cells may negatively affect prognosis | Zirakzadeh et al., 2020 |
ccRCC, clear cell renal cell cancer; DSS, disease-specific survival; ICB, immune check-point blocker; IGKC, immunoglobulin K constant domain; RFS, relapse-free survival; TIL, tumor-infiltrating lymphocytes.