The research, reported in Nature Immunology, gives new details on lymph node-like structures known as tertiary lymphoid structures. These structures, which are clusters of well-organised immune B and T cells, are present in some patients receiving immune checkpoint inhibitors, which are substances that restore the body’s natural defence against cancer and are linked to improved treatment outcomes.
Yarchoan and his counterparts have earlier performed the first clinical trial of immunotherapy for hepatocellular carcinoma before surgery. They identified that immunotherapy targeting more tertiary structures reduced tumour volume, and cancer recurrence after surgery was minimal for developed tertiary structures.
Tumours lacking these structures on the contrary underwent no regression and tended to recur after the operation. Secondary structures that developed in the centre of tumours rather than immediately around the perimeter were especially helpful.
When the investigators were studying the change of biopsies taken before immunotherapy and after immunotherapy they observed that the patients who developed these structures had what seemed to be ‘progenitors’ of Tertiary Lymphoid Structures before initiating the therapy.
When the study’s lead author Daniel Shu, M.D., who was then a medical oncology fellow at Johns Hopkins, looked at the areas where the patients’ tumours had been cleared, he found a change in the residual tertiary lymphoid structures.
Thus, in tumours where immunotherapy seemed to have the biggest impact, we observed another type of tertiary lymphoid structure that was previously undescribed. In this form, there was scattering of B cells and one can see the so-called T cell areas where T cells are activated to recognize antigens, Shu, Universities of Maryland School of Medicine.
The same patients benefit from immunotherapy given in this way most likely, for this reason also; And, there is still so much more to be done, but as a hypothesis what we have observed is that perhaps this is a stage four of tertiary lymphoid structure that may account for long-term outcomes we are now starting to see in these patients, Shu concludes.
They also aim to do the same regarding combinations of immunotherapies or any other pre surgical therapies on patients with regards to tertiary lymphoid structure formation.
It also may also extend to other cancers because of this new form of tertiary lymphoid structure, and the authors observed it in the other two types of tumours that are sensitive to immunotherapy.
Reference: Johns Hopkins Medicine. Lymph Node-Like Structures May Trigger the Demise
