Skip to main content
Erschienen in: Medical Oncology 3/2018

01.03.2018 | Original Paper

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

verfasst von: Anton Uryvaev, Maria Passhak, Dov Hershkovits, Edmond Sabo, Gil Bar-Sela

Erschienen in: Medical Oncology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

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.
Literatur
3.
Zurück zum Zitat Ladányi A, Somlai B, Gilde K, Fejös Z, Gaudi I, Tímár J. T-Cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Clin Cancer Res. 2004;10:521–30.CrossRefPubMed Ladányi A, Somlai B, Gilde K, Fejös Z, Gaudi I, Tímár J. T-Cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. Clin Cancer Res. 2004;10:521–30.CrossRefPubMed
4.
7.
Zurück zum Zitat Hiraoka K, Miyamoto M, Cho Y, Suzuoki M, Oshikiri T, Nakakubo Y, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer. 2006;94:275–80.CrossRefPubMedPubMedCentral Hiraoka K, Miyamoto M, Cho Y, Suzuoki M, Oshikiri T, Nakakubo Y, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer. 2006;94:275–80.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.CrossRefPubMedPubMedCentral Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–7.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–33.CrossRefPubMed Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823–33.CrossRefPubMed
28.
Zurück zum Zitat Zakharia Y, Drabick JJ, Khleif S, McWilliams RR, et al. Updates on phase 1b/2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus checkpoint inhibitors for the treatment of unresectable stage 3 or 4 melanoma. J Clin Oncol. 2016;34:suppl; abstr 3075. Status—Recruiting, Phase of Trial: Phase I/II Latest Information Update: 07 Sep 2017. Zakharia Y, Drabick JJ, Khleif S, McWilliams RR, et al. Updates on phase 1b/2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus checkpoint inhibitors for the treatment of unresectable stage 3 or 4 melanoma. J Clin Oncol. 2016;34:suppl; abstr 3075. Status—Recruiting, Phase of Trial: Phase I/II Latest Information Update: 07 Sep 2017.
Metadaten
Titel
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
verfasst von
Anton Uryvaev
Maria Passhak
Dov Hershkovits
Edmond Sabo
Gil Bar-Sela
Publikationsdatum
01.03.2018
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 3/2018
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-018-1080-0

Weitere Artikel der Ausgabe 3/2018

Medical Oncology 3/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.