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G.D. Sckisel

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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-036 - Peripheral Blood Immunophenotype Changes Following Thoracic Stereotactic Ablative Radiotherapy (ID 2282)

      09:30 - 17:00  |  Author(s): G.D. Sckisel

      • Abstract
      • Slides

      Stereotactic ablative radiotherapy (SAR) is a standard therapy for early stage, medically inoperable non-small cell lung cancer (NSCLC) and select metastatic tumors. Strategies combining SAR and immune checkpoint inhibitors are of great interest in potentially augmenting anti-tumor immune response, and prospective trials evaluating SAR/immunotherapy combinations are underway. However, the systemic immune response profile following SAR is poorly defined. Better understanding of the systemic immune response following SAR should allow optimization of SAR/immunotherapy protocols. We performed pre and 1 week post-SAR immune profiling on patients undergoing lung SAR, focusing on central memory T-cells which have been implicated as important mediators of systemic anti-tumor immune responses.

      Patients are actively accruing to an IRB approved protocol examining systemic immunophenotype changes following SAR for early stage (T1-2N0) NSCLC or metastatic lesions to the lung. Patients underwent collection of 30 cc blood by venipuncture immediately prior to and at 1 week post-SAR to a median dose of 50 Gy (range: 50-54 Gy) over 5 fractions (range: 3-5 fractions). Immunophenotyping of peripheral blood mononuclear cells (pbmc’s) was performed using flow cytometric analysis. Central Memory T-cells were defined as CD62L+ and CD45RA- subsets of CD4+ or CD8+ T-cells. Changes pre-treatment to post-treatment were compared across the cohort using a paired T-test.

      To date eleven NSCLC patients have accrued, and evaluable pre- and post-SAR specimens are available for six, all with early stage NSCLC (T1=4, T2=2, synchronous primaries =1). At one week post-SAR increases in systemic central memory CD4+ T-cells were observed in 4/6 patients and increases in systemic central memory CD8+ T-cells were observed in 3/6 patients with substantial (up to 10-fold) increases observed in some patients. Across the cohort the percent of circulating memory CD4+ T-cells increased from 1.9% pre-SAR to 3.1% post-SAR (p=0.06, Figure 1) and the percent of circulating memory CD8+ T-cells increased from 0.3% pre-SAR to 0.5% post-SAR (p=0.34, Figure 1).

      Our preliminary data in a limited patient cohort suggest lung SAR may induce systemic upregulation of circulating central memory T-cells which may be important mediators of the anti-tumor immune response. As more patients accrue, additional post-treatment time points are evaluated, and further analyses including cytokine/chemokine signatures are performed, we aim to better define systemic immunophenotype changes induced by lung SAR, assess how these changes relate to treatment toxicity and efficacy, and whether they can predict which patients will most likely benefit from the addition of immunotherapy to SAR. Figure 1

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