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The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma

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Abstract

Immunotherapy plays an important role in cancer treatment. Biomarkers that can predict response, including tumor-infiltrating lymphocytes (TILs), are in the spotlight of many studies. This cohort study was designed to evaluate the role of CD4+ and CD8+ TILs as predictive factors for response to anti PD-1 treatment in patients with metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma. We evaluated the expression of CD4+ and CD8+ TILs in tissue samples of 56 patients with metastatic NSCLC or melanoma treated with anti-PD1 immunotherapy. The study included 30 patients with melanoma and 26 with NSCLC. An association was found between CD8+/CD4+ TILs ratio and response to anti-PD1 treatment in both cancers. Regarding melanoma patients, ratios of CD8+/CD4+ lower than 2 predicted lack of response to treatment (0%) (p = 0.006), while CD8+/CD4+ ratios higher than 2.7 had an 81.3% response rate (p = 0.0001). In addition, we found that the presence of more than 1900/mm2 of CD8+ lymphocytes in the melanoma tumor predicted a 90% response to therapy. In the metastatic NSCLC group, tumors with CD8+ lymphocyte count under 886/mm2 showed low response rates (16.7%, p = 0.046). When the CD8+ lymphocyte count was in the range of 886-1899/mm2, the response rate was high (60%, p = 0.017). In CD8+/CD4+ ratios lower than 2, the response rate was low (13.3%), and in ratios higher than 2, response rates ranged between 43 and 50% (p = 0.035). The use of CD8+/CD4+ TILs ratios in tumor biopsies may predict response to anti-PD1 treatment in metastatic melanoma and NSCLC.

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Acknowledgement

Supported in full by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme (Israel-1996) Company Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Israel-1996) Company Ltd.

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Authors and Affiliations

  1. Division of Oncology, Rambam Health Care Campus, Haifa, Israel

    Anton Uryvaev, Maria Passhak & Gil Bar-Sela

  2. Pathology Department, Rambam Health Care Campus, Haifa, Israel

    Edmond Sabo

  3. Department of Pathology, Sourasky Medical Center, Tel Aviv, Israel

    Dov Hershkovits

  4. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Edmond Sabo & Gil Bar-Sela

  5. Integrated Oncology and Palliative Care Unit, Rambam Health Care Campus, POB 9602, 31096, Haifa, Israel

    Gil Bar-Sela

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  1. Anton Uryvaev
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Correspondence to Gil Bar-Sela.

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Uryvaev, A., Passhak, M., Hershkovits, D. et al. The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma. Med Oncol 35, 25 (2018). https://doi.org/10.1007/s12032-018-1080-0

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