Oncotarget

Research Papers:

Intratumoral immune-biomarkers and mismatch repair status in leiyomyosarcoma -potential predictive markers for adjuvant treatment: a pilot study

Jonathan E. Cohen, Feras Eleyan, Aviad Zick, Tamar Peretz and Daniela Katz _

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Oncotarget. 2018; 9:30847-30854. https://doi.org/10.18632/oncotarget.25747

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Abstract

Jonathan E. Cohen1, Feras Eleyan1, Aviad Zick1, Tamar Peretz1 and Daniela Katz2

1Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

2Institute of Oncology, Assaf Harofeh Medical Center Zrifin, Beer Yaacov, Israel

Correspondence to:

Daniela Katz, email: katzd@asaf.health.gov.il

Keywords: leiomyosarcoma; programed cell death ligand-1; CD8; mismatch repair deficiency; survival

Received: August 09, 2017     Accepted: June 23, 2018     Published: July 20, 2018

ABSTRACT

Leiomyosarcoma is the second most frequent soft-tissue sarcoma. Tumor lymphocytic infiltration (TIL) and programed cell death ligand-1 (PD-L1) have been associated with prognosis in different malignancies while DNA mismatch-repair deficiency (MMR-D) has been associated with response to check-point inhibitors. In this pilot study, we sought to examine TIL, PD-L1 and mismatch-repair (MMR) protein expression in 11 leiomyosarcoma and its association with outcome as potential biomarkers for adjuvant treatment.

Eleven primary leiomyosarcoma archived-tissues were analyzed for expression of MMR proteins (MSH2, MLH1, MSH6 and PSM2), PD-L1 expression and PD-1, CD3 or CD8.

MMR-D was detected in tumor tissue from 2/11 leiomyosarcoma patients. CD3 T-cells were present in all samples, whereas CD8 staining was positive in all but one. PDL-1 was positive in 4/11 and PD-L1 in 6/11. Interestingly, the three patients with the poorest outcome had strongly positive staining for PD-L1 and CD8 while in the two patients who are alive and recurrence-free, both PD-L1 and CD8 infiltration were lacking.

We found an association between tumor infiltrating CD8 cytotoxic lymphocytes, strong PD-L1 staining and survival; suggesting a role as biomarkers for treatment decisions regarding peri-operative chemotherapy. We also identified MMR-D in two patients with leiomyosarcoma comprising 18% of our sample.


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