Large-scale group genetic counseling: Evaluation of a novel service delivery model in a Canadian hereditary cancer clinic.

Increasing demand for genetic services has led to the development of streamlined genetic counseling (GC) models. We piloted large-scale group pre-test GC with up to 50 patients per group and compared this to a traditional one-on-one approach. Patients referred to the British Columbia (BC) Cancer Hereditary Cancer Program were eligible if they had: (a) family history meeting our program's referral criteria; (b) no relevant personal history of cancer; (c) no prior genetic testing in the family; and (d) no living testable relative in BC.

A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity.

Tumor-targeted chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR-T cells) have demonstrated striking clinical success, but their use has been associated with a constellation of toxicities. A better understanding of the pathogenesis of these toxicities is required to improve the safety profile of CAR-T cells. Herein, we describe a xenograft model of off-tumor CAR-T cell-associated toxicity.

Molecular Subtype Not Immune Response Drives Outcomes in Endometrial Carcinoma.

Purpose: Tumors with high mutation load are thought to engender stronger immune responses, which in turn promote prolonged patient survival. To investigate this, we assessed tumor-infiltrating lymphocytes (TILs) and immunosuppressive factors across the 4 molecular subtypes of endometrial cancer, which have characteristic mutation rates ranging from low to ultra-high.

Experimental Design: A total of 460 endometrial cancers were stratified by ProMisE (Proactive Molecular Risk Classifier in Endometrial cancer) into 4 molecular subtypes: mismatch repair-deficient (MMRd), mutant (POLE), p53 abnormal (p53abn), and p53 wild-type (p53wt).

The chimeric TAC receptor co-opts the T cell receptor yielding robust anti-tumor activity without toxicity.

Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing T cells to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here the authors show that the T cell antigen coupler (TAC), a chimeric receptor that co-opts the endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared with past-generation CARs. TAC-engineered T cells induce robust and antigen-specific cytokine production and cytotoxicity in vitro, and strong anti-tumor activity in a variety of xenograft models including solid and liquid tumors.

PD-L1 and intratumoral immune response in breast cancer.

Purpose: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance.

Methods: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype.

CD103 and Intratumoral Immune Response in Breast Cancer.

Purpose: CD103 is expressed in several immune cell types but in the context of the intratumoral immune response may be most important as a marker of antigen-activated CD8 T cells.

Methods: We have examined the prognostic significance of CD103 TILs in breast cancer by IHC in a cohort of 424 breast cancer patients.

Results: CD103 TILs were present in all subtypes but were more abundant in ER-negative tumors where CD103 TILs were preferentially localized to the intraepithelial compartment.