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LAG-3 and GAL-3 in Endometrial Carcinoma: Emerging Candidates for Immunotherapy.
- Source :
-
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists [Int J Gynecol Pathol] 2020 May; Vol. 39 (3), pp. 203-212. - Publication Year :
- 2020
-
Abstract
- LAG-3 is an immunosuppressive checkpoint molecule expressed on T cells. One of its ligands, GAL-3, can promote the progression of malignancy and has been identified on tumor cells. Both LAG-3 and GAL-3 are the targets of emerging immunotherapies, but have not been well-studied in endometrial carcinomas. LAG-3, CD3, and GAL-3 immunohistochemistry was performed on 75 endometrial cancers (25 nonmethylated mismatch repair-deficient, 25 MLH1-hypermethylated mismatch repair-deficient, and 25 mismatch repair-intact). LAG-3 and CD3 lymphocytes were averaged per high-power field. Tumoral GAL-3 expression was semiquantitatively scored. Tumor-infiltrating lymphocyte expression of LAG-3 and CD3 were positively correlated (Spearman ρ=0.521, P<0.001) and greater in mismatch repair-deficient compared with mismatch repair-intact tumors (LAG-3: P<0.001; CD3: P<0.001). The majority (64%) of endometrial carcinomas demonstrated ≥1% tumoral GAL-3 expression, with higher rates in mismatch repair-deficient versus intact tumors at the ≥1% (80% vs. 32%, P<0.001) and the ≥5% thresholds (52% vs. 16%, P=0.003). At the ≥5% threshold, nonmethylated mismatch repair-deficient cancers were more likely than intact tumors carcinomas to express GAL-3 (60% vs. 4/25 16%, P=0.003). LAG-3 lymphocytes were positively correlated with GAL-3 expression in nonmethylated mismatch repair-deficient endometrial carcinomas only (Spearman ρ=0.461, P=0.020). LAG-3 tumor-associated lymphocytes and GAL-3 neoplastic cells are common in endometrial carcinomas, particularly in nonmethylated mismatch repair-deficient cancers. This supports a role for immunotherapies targeting LAG-3 and/or GAL-3 in a subset of endometrial carcinomas, potentially in concert with other checkpoint inhibitors.
- Subjects :
- Antigens, CD genetics
Blood Proteins genetics
Brain Neoplasms pathology
CD3 Complex genetics
CD3 Complex metabolism
Colorectal Neoplasms pathology
DNA Mismatch Repair genetics
Endometrial Neoplasms pathology
Female
Galectins genetics
Humans
Ligands
Lymphocytes, Tumor-Infiltrating pathology
Neoplastic Syndromes, Hereditary pathology
Lymphocyte Activation Gene 3 Protein
Antigens, CD metabolism
Blood Proteins metabolism
Brain Neoplasms therapy
Colorectal Neoplasms therapy
Endometrial Neoplasms therapy
Galectins metabolism
Immunotherapy
Neoplastic Syndromes, Hereditary therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7151
- Volume :
- 39
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
- Publication Type :
- Academic Journal
- Accession number :
- 32267656
- Full Text :
- https://doi.org/10.1097/PGP.0000000000000608