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Manipulation of tumour-infiltrating B cells and tertiary lymphoid structures: a novel anti-cancer treatment avenue?

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Abstract

Combining different standard therapies with immunotherapy for the treatment of solid tumours has proven to yield a greater clinical benefit than when each is applied separately; however, the percentage of complete responses is still far from optimal, and there is an urgent need for improved treatment modalities. The latest literature data suggest that tertiary lymphoid structures (TLS), previously shown to correlate with the severity of autoimmune diseases or transplant rejection, are also formed in tumours, have a significant beneficial effect on survival and might reflect the generation of an effective immune response in close proximity to the tumour. Thus, the facilitation of TLS formation in tumour stroma could provide novel means to improve the efficiency of immunotherapy and other standard therapies. However, little is known about the mechanisms regulating the formation of tumour-associated TLS. Studies of chronic inflammatory diseases and transplant rejection have demonstrated that TLS formation and/or function requires the presence of B cells. Additionally, the infiltration of B cells into the tumour stroma has been demonstrated to be a significant prognostic factor for improved survival in different human tumours. This suggests that B cells could play a beneficial role in anti-tumour immune response not only in the context of antibody production, antigen presentation and Th1-promoting cytokine production, but also TLS formation. This review focuses on the latest discoveries in tumour-infiltrating B cell functions, their role in TLS formation and relevance in human tumour control, revealing novel opportunities to improve cancer therapies.

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Abbreviations

APC:

Antigen presenting cell

CTL:

Cytotoxic T lymphocyte

DC:

Dendritic cell

DN:

Double negative

ER:

Estrogen receptor

FDC:

Follicular dendritic cell

HEV:

High endothelial venule

HR:

Hazard ratio

Ig:

Immunoglobulin

IGKC:

Immunoglobulin kappa chain

ILF:

Isolated lymphoid follicle

LN:

Lymph node

LT:

Lymphotoxin

LTi cell:

Lymphoid tissue inducer cell

LTo cell:

Lymphoid tissue organiser cell

NK cell:

Natural killer cell

NSCLC:

Non-small-cell lung cancer

PDAC:

Pancreatic ductal adenocarcinoma

SLO:

Secondary lymphoid organ

TFH cell:

T follicular helper cell

Th cell:

T helper cell

TIB cell:

Tumour-infiltrating B cell

TLS:

Tertiary lymphoid structure

Treg cell:

T regulatory cell

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Acknowledgments

This work was supported by the European Regional Development Fund (ERDF) project No 2010/0231/2DP/2.1.1.1.0/10/APIA/VIAA/044.

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The authors declare that they have no conflict of interest.

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  1. Latvian Biomedical Research and Study Centre, Ratsupites 1, Riga, 1067, Latvia

    Karīna Siliņa, Undīne Rulle, Zane Kalniņa & Aija Linē

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  1. Karīna Siliņa
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  2. Undīne Rulle
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Correspondence to Karīna Siliņa.

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Siliņa, K., Rulle, U., Kalniņa, Z. et al. Manipulation of tumour-infiltrating B cells and tertiary lymphoid structures: a novel anti-cancer treatment avenue?. Cancer Immunol Immunother 63, 643–662 (2014). https://doi.org/10.1007/s00262-014-1544-9

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