ABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is known to have a heterogeneous desmoplastic tumour microenvironment (TME) with a large number of immunosuppressive cells. Recently, high B-cell infiltration in PDAC has received growing interest as a potential therapeutic target. METHODS: Our literature review summarises the characteristics of tumour-associated tertiary lymphoid structures (TLSs) and highlight the key studies exploring the clinical outcomes of TLSs in PDAC patients and the direct effect on the TME. RESULTS: The location, density and maturity stages of TLSs within tumours play a key role in determining the prognosis and is a new emerging target in cancer immunotherapy. DISCUSSION: TLS development is imperative to improve the prognosis of PDAC patients. In the future, studying the genetics and immune characteristics of tumour infiltrating B cells and TLSs may lead towards enhancing adaptive immunity in PDAC and designing personalised therapies.
ABSTRACT
The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.
ABSTRACT
Gallstone ileus is an uncommon cause of intestinal obstruction and occurs following the formation of a cholecystoenteric fistula, permitting passage of gallstones into the gastrointestinal tract. Impaction of a gallstone in the sigmoid colon is rare and is usually at sites of previous colonic disease. Definitive management can be challenging due to the advanced age and co-morbidity usually seen in this group of patients. We describe a patient successfully managed with on-table endoscopy and, under local anaesthetic, the formation of a left iliac fossa trephine loop colostomy, permitting an enterolithotomy to deliver the stone whilst accommodating for severe pre-existing distal sigmoid diverticular disease. A review of the literature identified various endoscopic and surgical treatments that, depending on local expertise and patient characteristics, can be considered on a case-by-case basis. We advocate the management described in this case for patients presenting with large bowel obstruction due to gallstone ileus, with a background of diverticular disease and who are not fit for general anaesthetic or formal bowel resection, as an alternative to medical palliation alone.
