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From 19 to 21 November 2022, BioCanRx held its first post-pandemic in-person Summit for Cancer Immunotherapy in Montreal, Canada. The meeting was well attended by patients, trainees, researchers, clinicians, and industry professionals, who came together to discuss the current state and future of biotherapeutics for cancer in Canada and beyond. Three plenaries, three keynote speakers, a lively debate, and panel discussions, together with poster sessions and a social event, made the event memorable and productive. The current state of cellular therapies, cellular engineering, clinical trials, and the role of the cancer microbiome were discussed in plenary session, and the patient voice was welcomed and present throughout the meeting, in large part due to the Learning Institute, a BioCanRx initiative to include patient partners in research. In this meeting review, we highlight the platform presentations, keynote speakers, debate combatants, panellists, and the patient perspective on the annual meeting., Competing Interests: The authors declare there are no competing interests.

Unlike other histological types of epithelial ovarian carcinoma, clear cell ovarian carcinoma (CCOC) has poor response to therapy. In many other carcinomas, expression of the hypoxia-related enzyme Carbonic anhydrase IX (CAIX) by cancer cells is associated with poor prognosis, while the presence of CD8 + tumor-infiltrating lymphocytes (TIL) is positively prognostic. We employed [ 18 F]EF5-PET/CT imaging, transcriptome profiling, and spatially-resolved histological analysis to evaluate relationships between CAIX, CD8, and survival in CCOC. Tissue microarrays (TMAs) were evaluated for 218 cases in the Canadian COEUR study. Non-spatial relationships between CAIX and CD8 were investigated using Spearman rank correlation, negative binomial regression and gene set enrichment analysis. Spatial relationships at the cell level were investigated using the cross K-function. Survival analysis was used to assess the relationship of CAIX and CD8 with patient survival for 154 cases. CD8 + T cell infiltration positively predicted survival with estimated hazard ratio 0.974 (95% CI 0.950, 1000). The negative binomial regression analysis found a strong TMA effect (p-value < 0.0001). It also indicated a negative association between CD8 and CAIX overall (p-value = 0.0171) and in stroma (p-value = 0.0050) but not in tumor (p-value = 0.173). Examination of the spatial association between the locations of CD8 + T cells and CAIX cells found a significant amount of heterogeneity in the first TMA, while in the second TMA there was a clear signal indicating negative spatial association in stromal regions. These results suggest that hypoxia may contribute to immune exclusion, primarily mediated by effects in stroma., (© 2023. The Author(s).)

Introduction: It is important for many research stakeholders to know how many biobanks exist. There are several potential data sources that might be expected to provide biobank numbers, such as institutions, research funders, and literature databases (e.g., PubMed), but in practice this information is rarely available and is hard to find. However, the maturation of several online health research biobank locators (also known as directories and catalogs) that relate to 12 countries and/or states has now provided some initial data to address the question of how many health research biobanks exist in relation to population size. Methods: We have analyzed four biobank locators: the Biobanking and Biomolecular Resources Research Infrastructure-European Research Infrastructure Consortium directory, the Canadian Tissue Repository Network locator, the Australian New South Wales Australia Health Pathology locator, and the UK Clinical Research Collaboration Tissue Directory. Results: We conclude that across these locators, and in those regions with potential for high research capacity as indicated by comparable gross domestic products, there are 11-30 health research biobanks/million population (2 large biobanks with >1000 samples and a further 9-28 are medium-small biobanks). Conclusion: Many locators were established primarily to increase utilization of biobanks. However, locators may be more useful in tracking the numbers of biobanks and in assisting funders and institutions to monitor research strategy and prevent unnecessary duplication of biobank resources.

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis-associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8 + tumour-infiltrating lymphocytes (CD8 + TILs), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOCs and 25% of ENOCs. We found no associations between ARID1A loss and outcomes, stage, age, or CD8 + TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p = 0.012) and was associated with MMRd (p < 0.001) and the presence of CD8 + TILs (p = 0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOCs we also observed an association with ARID1A loss-of-function mutation as a result of small indels (p = 0.035, versus single nucleotide variants). In ENOC, the association with ARID1A loss, CD8 + TILs, and age appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8 + TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. © 2021 The Pathological Society of Great Britain and Ireland., (© 2021 The Pathological Society of Great Britain and Ireland.)

Impactful biobanking is underpinned by quality assurance and standardization. Several general biobank standards exist that can be associated with programs to provide different levels of conformity assessment, including the Canadian Tissue Repository Network (CTRNet) Certification program and the International Organization for Standardization (ISO) 20387 and accreditation bodies. We examined the CTRNet Required Operational Practices (2017) and ISO 20387 (2018), to compare them. Although the organization of each standard is different, both describe a set of discrete requirements (elements or subclauses) that comprise the standards that are contained in sections called chapters (CTRNet) or clauses (ISO). The standards have a similar number of requirements (CTRNet: 362, ISO: 322). To compare these standards, we reclassified the requirements in the ISO standard into 13 categories based on a combination of the chapter headings used in the ISBER and NCI Best Practices that represent important areas of biobanking activity. This categorization of requirements showed that each standard has a different emphasis reflected in different densities of requirements within distinct areas of biobanking. The ISO standard emphasizes Quality Management Systems whereas the CTRNet standard has an even coverage across the full spectrum of biobanking areas, including activities that are relevant to participant enrollment. Nevertheless, ∼60% of the requirements in the CTRNet standard match with those of the ISO standard. We conclude that these two standards have much in common but recommend that individual biobanks consider each standard carefully in the context of the purpose, focus, scale, and scope of their biobank to determine the appropriate standard to be followed.

The Canadian Tissue Repository Network (CTRNet) Biobank Certification Program was first launched in 2011 to foster translational research through improved access to high quality biospecimens. This was accomplished by creating and providing biobank education and through the establishment and deployment of common standards to harmonize biospecimen quality and approaches to governance. The CTRNet program comprises registration and certification steps as two linked phases. In the two-step registration phase, the biobank is registered into the system, and an individual completes an overview educational module. In the subsequent certification phase, biobanks undergo a seven-step process, including inviting team members, assigning and completing relevant education modules, uploading documents, and undergoing a documentation audit. As of June 2018, there were 251 biobanks engaged in the CTRNet program, 193 had completed registration, and 40 were fully certified. Over 3/4 of these biobanks completed registration within a week and over 1/3 completed certification within a month. Among registered biobanks, 163 were associated with North American institutions, while 30 were from other international locations, including Australia, Europe, and Asia. The CTRNet program enables biobanks to adopt standards with a flexible approach to accommodate different types of biobanks and a measured investment of effort, creating the foundation for increased access to high quality biospecimens.

Background: Establishing the importance of biobanking in cancer research is important for research funders and for planning health research infrastructure. This study delineates the importance of biobanking to the cancer research landscape in Canada and relative to other forms of health research infrastructure., Methods: The Cancer Research Society (CRS) is a Canadian organization with a broad mission and national portfolio that funds studies across the spectrum of cancer research. We selected all 35 investigators who received CRS grants in the 2010/11 competition and then analyzed their publications from 2010 to 2014. Articles were categorized by overall research area, acknowledged source of funding, specific scientific focus, and the presence of any data that involved an 'indicator' (human biospecimens, cell lines, animal models, advanced microscopy, flow cell sorters, and next generation sequencing) of dependence on different kinds of health research infrastructures. Publications involving biobanking and utilizing biospecimens were further classified by biospecimen provenance and type of biospecimen used., Results: These investigators generated 502 (from a total of 749) papers that were related to the field of cancer research. Amongst 445 papers that contained primary data, we found no significant differences between CRS funded and 'other funded' papers in terms of biospecimen use, which occurred in 38% of articles. Overall biospecimens were mostly obtained directly from patients (17%), or indirectly from biorepositories (31%) and hospitals (46%). The proportions of studies using other tools was as follows: 54% cell lines, 32% animal models, 14% advanced microscopy, 14% flow sorters, and 8% next generation sequencing. The spectrum of research was very similar to the overall profile of cancer research in Canada in 2010., Conclusions: This study suggests that biorepositories that coordinate the activity of biobanking rank amongst the most important of established health research infrastructures as contributors to research publications.