No abstract

A prospective study explored the heterogeneous nature of metastatic melanoma using Multiplex immunohistochemistry (IHC) and flow cytometry (FACS). Multiplex IHC data quantitated immune subset number present intra-tumoral (IT) vs the tumor stroma, plus distance of immune subsets from the tumor margin (TM). In addition, mIHC showed a close association between the presence of IT CD8+ T cells and PDL1 expression in melanoma, which was more prevalent on macrophages than on melanoma cells. In contrast, FACS provided more detailed information regarding the T cell subset differentiation, their activation status and expression of immune checkpoint molecules. Interestingly, mIHC detected significantly higher Treg numbers than FACS and showed preferential CD4+ T cell distribution in the tumor stroma. Based on the mIHC and FACS data, we provide a model which defines metastatic melanoma immune context into four categories using the presence or absence of PDL1+ melanoma cells and/or macrophages, and their location within the tumor or on the periphery, combined with the presence or absence of IT CD8+ T cells. This model interprets melanoma immune context as a spectrum of tumor escape from immune control, and provides a snapshot upon which interpretation of checkpoint blockade inhibitor (CBI) therapy responses can be built.

No abstract

No abstract

No abstract

Lymphocele is a common wound complication of sentinel lymph node biopsy (SLNB). The surgical technique may play a key role in lymphocele formation. This study compared rates of postoperative lymphocele formation by different surgical techniques (Harmonic Scalpel [HS], LigaSure [LS], and traditional electrocautery with clips) after SLNB in the groin or axilla for the staging of clinically node-negative cutaneous melanoma. Patients were selected by convenience sample from a single-institution, single-surgeon, prospectively collected melanoma database over a 27-month period. One hundred fifty consecutive patients underwent SLNB, 70 with clips, 37 with HS, and 43 with LS. The median number of nodes removed was two and did not vary significantly between groups. Twenty-three lymphoceles occurred for an overall rate of 15 per cent; rates were 9.9 and 26.5 per cent for the axilla and groin, respectively. Sixteen (70%) were aspirated for size or symptoms; lymphoceles after groin SLNB were significantly (P = 0.03) more likely to require aspiration. Lymphocele rates for the clip, HS, and LS groups were 20.0, 18.9, and 4.7 per cent, respectively. The differences between the LS and other groups were statistically significant. Use of the LS may lead to lower lymphocele rates after groin and axillary SLNB compared with electrocautery and clips.

Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. Methods: We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Results: Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen. CAR-TIL produced greater amounts of IFN compared with parental TIL, when co-cultured with Her2 expressing tumor lines, including autologous melanoma tumor lines, although no consistent increase in cytotoxicity by TIL was afforded by expression of a CAR. Results of an in vivo study in NSG mice demonstrated tumor shrinkage when CAR-TILs were used in an adoptive cell therapy protocol. Conclusion: Potential limitations of transduced TIL in our study included limited proliferative potential and a terminally differentiated phenotype, which would need addressing in further work before consideration of clinical translation.

Background:The Ontario Breast Screening Program was expanded in 2011 to offer annual MRI and mammography to women with high-risk genetic mutations (e.g., BRCA1/2) and women with strong family histories and ≥25% estimated lifetime risk of breast cancer. Data to support high-risk screening is less clear in the nonmutation carrier group, as MRI has lower specificity among this population. The potential unintended consequences may be considerable and need to be explored. We aimed to describe the frequency of abnormal screens and biopsies.Methods: Demographic surveys and chart review consent were sent to a sample of 441 individuals enrolled in a high-risk screening program at two tertiary care hospitals in Toronto, Ontario. Retrospective cross-sectional chart review was undertaken for clinicopathologic data. The frequencies of abnormal screens and biopsies were calculated.Results: One hundred sixty-nine nonmutation carriers were included. The majority were white, employed, and highly educated. The median International Breast Cancer Intervention Study lifetime risk of breast cancer was 28.0% (range 24.5%-89.0%). 108 individuals (64%) experienced at least 1 abnormal screen and 13 (8%) had 3 or more over a median 3 years of screening (range 1-6 years). Of 55 biopsies, 3 (5.5%) were malignant. The cancer detection rate was 8.4/1000 screens (95% CI 3.2-22.4).Conclusions: An MRI-based screening program for nonmutation carriers was effective at diagnosing breast cancer. However, this population experienced a high rate of abnormal screens and intervention. Further research is needed to improve the performance of MRI-based screening in these women.