Faculty Bibliography

Intratumor heterogeneity (ITH) of T cell receptor (TCR) repertoire in different T-cell subsets and locations in lung adenocarcinomas was unclear. Here, we investigated percentages and TCR repertoire of freshly isolated CD4⁺ and CD8⁺ tumor infiltrating lymphocytes (TILs) in tumor centers and margins by flow cytometry on 80 tumor samples from 20 patients and high-throughput TCR sequencing on 27 and 25 samples of CD4⁺ and CD8⁺ TILs from seven patients. Our results demonstrated that amount and TCR repertoire diversity of CD4⁺ TILs were significantly higher than those of CD8⁺ TILs and moreover substantial ITH regarding amount and TCR repertoire of CD4⁺ and CD8⁺ TILs were observed. Additionally, ITH of CD4/CD8 T-cell ratio and CD8⁺ TIL repertoire across center regions was lower than that across margin regions. The amount and TCR repertoire ITH of CD4⁺ and CD8⁺ TILs and mean clonality of CD8⁺ TILs in tumor centers were associated with relapse. Our study provides insights into amount and TCR repertoire ITH of CD4⁺ and CD8⁺ TILs in tumor centers and margins as well as corresponding association with prognosis in lung adenocarcinoma patients, suggesting potential clinical significance of TCR repertoire.

CONTEXT/BACKGROUND:- In Gleason score GS (7) prostate cancers, the quantity of Gleason pattern 4 (GP 4) is an important prognostic factor and influences treatment decisions. Magnetic resonance imaging (MRI)-targeted biopsy has been increasingly used in clinical practice. OBJECTIVE:- To investigate whether MRI-targeted biopsy may detect GS 7 prostate cancer with greater GP 4 quantity, and whether it improves biopsy/radical prostatectomy GS concordance. DESIGN/METHODS:- A total of 243 paired standard and MRI-targeted biopsies with cancer in either standard or targeted or both were studied, 65 of which had subsequent radical prostatectomy. The biopsy findings, including GS and tumor volume, were correlated with the radical prostatectomy findings. RESULTS:- More prostate cancers detected by MRI-targeted biopsy were GS 7 or higher. Mean GP 4 percentage in GS 7 cancers was 31.0% ± 29.3% by MRI-targeted biopsy versus 25.1% ± 29.5% by standard biopsy. A total of 122 of 218 (56.0%) and 96 of 217 (44.2%) prostate cancers diagnosed on targeted biopsy and standard biopsy, respectively, had a GP 4 of 10% or greater ( P = .01). Gleason upgrading was seen in 12 of 59 cases (20.3%) from MRI-targeted biopsy and in 24 of 57 cases (42.1%) from standard biopsy ( P = .01). Gleason upgrading correlated with the biopsy cancer volume inversely and GP 4 of 30% or less in standard biopsy. Such correlation was not found in MRI-targeted biopsy. CONCLUSIONS:- Magnetic resonance imaging-targeted biopsy may detect more aggressive prostate cancers and reduce the risk of Gleason upgrading in radical prostatectomy. This study supports a potential role for MRI-targeted biopsy in the workup of prostate cancer and inclusion of percentage of GP 4 in the prostate biopsy reports.

Recent successes in tumour immunotherapies have highlighted importance of tumour immunity. However, most previous studies to date have focused on T cell immune response, although B cells are key players in the core immune network and are associated with T-cell immune response. Based on our previous study delineating T cell receptor (TCR) repertoire in seven patients with esophageal squamous cell carcinoma (ESCC), this study profiled BCR repertoire of multiple tumour regions, adjacent normal tissue and blood from the same seven patients to reveal characteristics of B cell immunity and relationship to TCR repertoire in ESCC patients. We found that intratumour B cell receptor (BCR) repertoire was significantly more oligoclonal than matched adjacent normal tissue or peripheral blood and moreover clonal amplification of B cells in multiple tumour regions was significantly heterogeneous, although clonal amplification of TCR repertoire across different tissue compartments and regions of the same tumour was similar. However, both BCR and TCR repertoires in tumour microenvironment were distinct from those in adjacent normal tissues and blood, and thus represented a group of B and T cells which were spatially confined to the tumour microenvironment and could react to tumour antigens. Additionally, B and T cell clones varying between different tumour regions showed intratumour heterogeneity of B and T cell immune response. Thus, multiple tumour biopsies could be essential to comprehensively delineate the adaptive immune response to an individual ESCC. These findings expand our understanding of adaptive antitumor immunity and shed more light on ESCC immunotherapy. This study provides insights into intratumour heterogeneity of BCR repertoire as well as difference and relationship between BCR and TCR repertoire in ESCC, expanding our understanding of adaptive antitumor immunity and ESCC immunotherapy.