Further functional studies of T cell populations would expand our understanding of T cell based immune therapies. Patients showing poor response show a TCR repertoire that is constantly changing potentially indicating that the tumor cells are not eliciting a strong T cell specific response. Therapy would allow these existing T-cells to overcome blockade by tumor cells. Conclusions: Patients that show positive response had TCR clones that were stable, which may indicate an existing immune related response towards their tumor. Loss of clonality and/or decrease in absolute numbers was observed in previous and later time points. Patients that showed poor response by irRC and Recist1.1 showed TCR clones that were in constant flux. A TNBC super responder showed dramatic increases in mean Shannon-Wiener index from 74 prior treatment to 1177 at first biopsy post treatment (34% decrease by irRC and 26% by Recist1.1 analysis) and achieved an index as high as 3516 in a subsequent biopsy (83% and 64% decrease by irRC and Recist 1.1 respectively). Results: Patient samples showing consistent positive responses as measured by irRC and Recist1.1 showed TCR clones persisting throughout all time points. Additionally the Shannon-Wiener diversity metric was calculated for each time point. TCR alpha and beta CDR3s were clonotyped for each sample, and profiles of clonotype proportions were tracked through time/serial biopsies. Blood draws were collected pre- and post-treatment and target lesion analysis was performed using immune-related response criteria (irRC) and Recist1.1. Methods: Total RNA from peripheral blood mononuclear cells (PBMCs) was extracted and used to generate sequencing libraries from five pancreatic cancer patients, four triple negative breast cancer (TNBC) patients and two squamous cell carcinoma (SCC+) patients. To study the prognostic significance of T cell repertoires as a biomarker of immune responses in cancer patients, we characterized TCR repertoires from peripheral blood using high throughput sequencing. Net diversity of TCR repertoires are altered in patients receiving immune checkpoint inhibitors. T cell receptors (TCRs) play a crucial role in adaptive immunity and anti-tumor immune responses. Background: Immune checkpoint inhibitors offer substantial clinical advantage to a subset of patients but predictive/novel prognostic indicators are still scarce. Subject: Please expand my repertoire of healthy, filling, lower carb dinners that I will love to eat Anonymous saute 1 pint cherry tomatoes in olive oil until blistered, and I usually break some uo for a bit of sauce once they are cooked.
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