Intratumoral immune-biomarkers and mismatch repair status in leiyomyosarcoma -potential predictive markers for adjuvant treatment: a pilot study
Autor: | Tamar Peretz, Feras Eleyan, Aviad Zick, Jonathan Cohen, Daniela Katz |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Oncology Leiomyosarcoma medicine.medical_specialty medicine.medical_treatment survival 03 medical and health sciences 0302 clinical medicine Internal medicine medicine programed cell death ligand-1 Chemotherapy mismatch repair deficiency business.industry CD8 leiomyosarcoma medicine.disease MSH6 030104 developmental biology MSH2 030220 oncology & carcinogenesis Primary Leiomyosarcoma Sarcoma business Adjuvant Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
DOI: | 10.18632/oncotarget.25747 |
Popis: | 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. |
Databáze: | OpenAIRE |
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