NorthWest Biotherapeutics Inc (NWBO)

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I ran across this a while back, but with all this renewed interest in Lymph Nodes, Migration and the like, I thought some might be interested in knowing that cancerous tumors often contain tertiary lymph node like structures that play a critical role in immunity and survival. (Note: One thing I wondered two or three years ago was whether dendritic cells somehow might express antigens to t-cells at the tumor site without migrating to the lymph nodes. I think it was a Nature article I read back then that made me think something else must be happening on some occasions.)

Anyway, here is a 2015 abstract on tertiary lymph structures. Following it is a link to a free article primarily discussing B cell response in tumors with TLS. These are fascinating times.

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337382/

Int Rev Immunol. 2015 Mar;34(2):123-33. doi: 10.3109/08830185.2015.1018416.
Tertiary lymphoid tissue in the tumor microenvironment: from its occurrence to immunotherapeutic implications.
Di Caro G1, Castino GF, Bergomas F, Cortese N, Chiriva-Internati M, Grizzi F, Mantovani A, Marchesi F.
Author information
Abstract
Recruitment of immune and inflammatory cells in the microenvironment of solid tumors is highly heterogeneous and follows patterns, varying according to the organ of origin and stage of disease, with critical roles in the process of cancer onset and progression. While adaptive cells are endowed with anti-tumor activities, inflammatory components of the immune infiltrate orchestrate an immunosuppressive microenvironment that reveals ambivalent functions of the immune contexture in the tumor milieu. The balance between opposing pro-tumoral and anti-tumoral immune pathways, which occur concomitantly in the tumor microenvironment, and the regulatory networks of these phenomena have been the target of several immunotherapeutic strategies. While the scarcity of adaptive immune effectors in tumors correlates with dismal prognosis, the pathways of activation of tumor-specific lymphocytes are yet to be fully elucidated. Recently, the occurrence of tertiary lymphoid tissue was revealed to be critical in mediating the dynamics of T cell recruitment and local activation of immune cells in the tumor microenvironment. Thus, tertiary lymphoid tissue assessment and targeting emerge as a promising approach for the design of novel prognostic immune signatures and immunotherapeutic strategies. The immunological behavior of tertiary lymphoid tissue, its occurrence in the tumor immune microenvironment and its clinical relevance are discussed here.

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337382/

Free article: here is the abstract:

Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity
Claire Germain,1,2,3 Sacha Gnjatic,4 and Marie-Caroline Dieu-Nosjean1,2,3,*

Abstract
It is now admitted that the immune system plays a major role in tumor control. Besides the existence of tumor-specific T cells and B cells, many studies have demonstrated that high numbers of tumor-infiltrating lymphocytes are associated with good clinical outcome. In addition, not only the density but also the organization of tumor-infiltrating immune cells has been shown to determine patient survival. Indeed, more and more studies describe the development within the tumor microenvironment of tertiary lymphoid structures (TLS), whose presence has a positive impact on tumor prognosis. TLS are transient ectopic lymphoid aggregates displaying the same organization and functionality as canonical secondary lymphoid organs, with T-cell-rich and B-cell-rich areas that are sites for the differentiation of effector and memory T cells and B cells. However, factors favoring the emergence of such structures within tumors still need to be fully characterized. In this review, we survey the state of the art of what is known about the general organization, induction, and functionality of TLS during chronic inflammation, and more especially in cancer, with a particular focus on the B-cell compartment. We detail the role played by TLS B cells in anti-tumor immunity, both as antigen-presenting cells and tumor antigen-specific antibody-secreting cells, and raise the question of the capacity of chemotherapeutic and immunotherapeutic agents to induce the development of TLS within tumors. Finally, we explore how to take advantage of our knowledge on TLS B cells to develop new therapeutic tools.