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, Daniela Katz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)30847-30854
Number of pages8
JournalOncotarget
Volume9
Issue number56
DOIs
StatePublished - 20 Jul 2018
Externally publishedYes

Keywords

  • CD8
  • Leiomyosarcoma
  • Mismatch repair deficiency
  • Programed cell death ligand-1
  • Survival

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