Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide with an overall survival rate, all stages combined, of still <10% at 5 years. The poor prognosis is attributed to challenges in early detection, a low opportunity for radical resection, limited response to chemotherapy, radiotherapy, and resistance to immune therapy. Moreover, pancreatic tumoral cells are surrounded by an abundant desmoplastic stroma, which is responsible for creating a mechanical barrier, preventing appropriate vascularization and leading to poor immune cell infiltration. Accumulated evidence suggests that PDAC is impaired with multiple “immune defects”, including a lack of high-quality effector cells (CD4, CD8 T cells, dendritic cells), barriers to effector cell infiltration due to that desmoplastic reaction, and a dominance of immune cells such as regulatory T cells, myeloid-derived suppressor cells, and M2 macrophages, resulting in an immunosuppressive tumor microenvironment (TME). Although recent studies have brought new insights into PDAC immune TME, its understanding remains not fully elucidated. Further studies are required for a better understanding of human PDAC immune TME, which might help to develop potent new therapeutic strategies by correcting these immune defects with the hope to unlock the resistance to (immune) therapy. In this review, we describe the main effector immune cells and immunosuppressive actors involved in human PDAC TME, as well as their implications as potential biomarkers and therapeutic targets.

The association between tumor necrosis factor inhibitors (TNFi) and malignancy in patients with inflammatory bowel disease (IBD) is not well understood. Our aim was to systematically evaluate the impact of TNFi use on risk of malignancy in IBD-patients in daily clinical practice. We searched Pubmed, Embase, and Scopus until March 1 ^st 2020 for observational cohort studies on adult IBD-patients reporting malignancy occurrence and TNFi use. Twenty-eight studies (20 retrospective and 8 prospective) were included, involving 298,717 IBD-patients. Mean age at inclusion ranged from 28 to > 65 years. Mean follow-up varied from 7 to 80 months. Infliximab was the most frequently used TNFi (13/28 studies, 46.4%), followed by adalimumab (3/28, 10.7%), while both infliximab and adalimumab were evaluated in 5 studies (17.8%). In total, 692 malignancies were diagnosed in IBD-patients treated with TNFi accounting for an overall occurrence of 1.0%. The most frequent malignancies were non-melanoma skin cancers (123/692, 17.8%), digestive malignancies (120/692, 17.3%), and hematological malignancies (106/692, 15.3%). The association between TNFi and malignancy was evaluated in 11 studies (39.3%): no significant association was found in 10 studies, while an increased risk of lymphoma in patients exposed to TNFi was reported in one study. TNFi treatment is not associated with an increased risk of malignancy in IBD-patients in real-life settings. Further large studies are needed to assess prognosis of patients exposed to TNFi and risk of recurrence or new cancers in subjects with personal malignancy history.

Patients with inflammatory bowel disease are at increased risk of colorectal cancer, which has worse prognosis than sporadic colorectal cancer. Until recently, understanding of pathogenesis in inflammatory bowel disease‐associated colorectal cancer was restricted to the demonstration of chromosomic/microsatellite instabilities and aneuploidy. The advance of high‐throughput sequencing technologies has highlighted the complexity of the pathobiology and revealed recurrently mutated genes involved in the RTK/RAS, PI3K, WNT, and TGFβ pathways, leading to potentially new targetable mutations. Moreover, alterations of mitochondrial DNA and the dysregulation of non‐coding sequences have also been described, as well as several epigenetic modifications. Although recent studies have brought new insights into pathobiology and raised the prospect of innovative therapeutic approaches, the understanding of colorectal carcinogenesis in inflammatory bowel disease and how it differs from sporadic colorectal cancer remains not fully elucidated. Further studies are required to better understand the pathogenesis and molecular alterations leading to human inflammatory bowel disease‐associated colorectal cancer.

Lymphoma is a dreaded complication of inflammatory bowel diseases (IBD). Knowledge about lymphoma in patients with IBD is limited to epidemiological data and risk factors description. We performed a systematic review to describe clinical characteristics and prognosis of lymphoma in patients with IBD. Electronic databases were searched up to 1 ^st June 2020. All published clinical characteristics of lymphoma occurring in patients with IBD were collected. Eleven studies were included. A total of 589 lymphomas were described in patients with IBD. As seen in de novo lymphoma, non-Hodgkin’s lymphoma (NHL) was the most common histological subtype (83.9%). Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma were the most represented NHL in patients with IBD (30% and 13% respectively). Two main differences were observed in comparison to de novo lymphoma: primary intestinal lymphoma (PIL) represented a large part of lymphoma in patients with IBD (22% to 75%) whereas mucosa-associated lymphoid tissue (MALT) lymphoma was under-represented. Epstein-Barr virus (EBV) positive status was observed in a large part of tumors (44 to 75%). Survival data of lymphoma in patients with IBD were similar to that of de novo lymphoma. This systematic review first highlights that PIL (especially DLBCL subtype) is significantly more frequent in patients with IBD and represents the most common entity. Conversely, MALT lymphoma is extremely rare in IBD population. However, the overall quality of the evidence is low. Further studies are required to better define lymphoma characteristics in patients with IBD.