A wide world of mechanisms leading to tumor immune evasion have emerged. Assessment of these mechanisms has relevance to immunotherapy applications.

Emerging cancer immunotherapy strategies are increasingly more sophisticated in promoting an anti-tumor immune response in patients. This presentation addresses developments in tissue-based cell profiling technologies that can reveal complex changes in tumor-immune infiltration and shifts in immune cell activity/polarity as it relates to preclinical development. In addition to providing insight into mechanisms of action, emerging signatures may provide direction for translational biomarkers that may improve clinical outcomes in early-phase trials.

The integrative field of immunology-MPE (molecular pathological epidemiology) is an emerging paradigm, and can investigate influences of the exposome (dietary, lifestyle, environmental, microbial, pharmacological, and other exposures) on tumor-immune interactions, thereby informing immunotherapy research. Using over 1500 colorectal cancer cases with rich data on immune response, whole exome sequencing, RNA-sequencing, tumor neoantigens, and clinical outcomes, proof-of-principle immunology-MPE studies have shown great promise for precision prevention and immuno-oncology.

While much work has focused on the tumor immune microenvironment of established cancers, little is known about the immune response to the earliest stages of tumor development. This talk will explore the immune microenvironment of neoplastic precursor lesions in the pancreas, focusing on pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms (IPMN) with emphasis on features predicting grade of dysplastic change and recurrence/progression to malignancy.

This presentation will discuss combining tissue and liquid biopsy to follow the patient’s tumor evolution and adding RNA gene expression profiling to DNA to expand clinical options for patients.

There are currently four precision medicine drugs which can be prescribed from two US FDA-approved CDx tests using ctDNA, and with many CDx submissions for plasma assays under the breakthrough designation indicates that plasma is increasing its impact in the clinical practice of precision medicine. The Japanese PMDA has approved the first NGS CDx plasma assay and many companies have announced PMA submissions of an NGS plasma assay for approval in the US which will be game changing for cancer patients.

High volume clinical laboratories need to accommodate a variety of specimen types, qualities, and quantities. This typically cannot be accomplished using a single method; we have validated a large hybrid-capture based panel and a small amplicon-based companion panel for low-input and/or low-quality DNA. This talk will discuss the decision-making process for panel design, both inter- and intra-laboratory. The large panel includes content shared across multiple institutions which have decided to utilize similar methodologies allowing for cross-validation.

Tiaki has created a discovery platform for identification, validation and development of therapeutic strategies. Implementation of the FirePlex assay in early target discovery has enabled identification of putative neuroinflammation program-enabling biomarkers. Zeev Gechtman, Abcam's technical product manager will present the Q&A session. 

Biomarkers are a critical component to advance therapeutic programs and to make informed decisions along the value chain. In Sanofi Translational Sciences, we utilize genomics, genetics, proteomics, molecular histology and informatics approaches to identify candidate biomarkers. This presentation will illustrate multi-pronged and integrated approaches to discover and qualify biomarkers for hand-off for use in development and in the clinic. Several biomarker case studies will be presented, illustrating different approaches and utilities of biomarkers, as well as key factors for success.

Clinical samples are precious and generally limited. There are ways to stretch specimens further, such as aliquoting, or provision of extracted nucleic acid or even data rather than FFPE sections to analyzing laboratories. However, there are considerations necessary to this approach, including careful specimen tracking, freeze/thaw stability, fit-for-purpose cross-validation, and assay limitations.

Advances in analytical instrumentation and reagents have afforded researchers the opportunity to interrogate post-translational modifications (PTMs) of protein biomarkers. Analysis of Tau and p181 Tau levels in CSF has been utilized in clinical trials to gain insight as a diagnostic compliment to PET scans, monitoring disease progression and response to therapeutic intervention. Incorporation of expanded Tau PTM analysis as part of a translational research strategy will be presented.

This presentation will discuss endogenous serum IgG antibodies to Clostridium difficile toxin B which are associated with protection against C. difficile infection recurrence.

PD-L1 immunohistochemistry (IHC) is a globally accepted predictive biomarker for the PD-1/PD-L1 axis blockade and is now deployed in most pathology laboratories. Although its appropriate implementation and interpretation are critical, it can be challenging due to the multiple antibody clones/platforms available and given the typically small samples provided. Thus, I will discuss important considerations on pre-analytical, analytical and post-analytical aspects of PD-L1 IHC mainly for lung cancer. These issues are not specific for PD-L1 IHC and need to be considered when co-developing a predictive IHC marker for an agent in clinical trials in general. I will also briefly touch upon other predictive biomarkers for immunotherapy.