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Updated: Oct 14, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
PD1/PDL1 expression is associated with increased TIM3 expression and tumor-infiltrating T lymphocytes in fibroblastic
1Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, 541199, China.
Purpose:
The combined therapy of inhibiting T cell immunoglobulin domain and mucin domain 3 (TIM3) and programmed cell death 1/programmed death-ligand 1 (PD1/PDL1) has shown encouraging therapeutic effects in some solid tumors. However, the expression of PD1/PDL1 and TIM3 in fibroblastic tumors is ill defined, which has limited the application of these immune checkpoint inhibitors in such tumors.
Methods:
Immunostaining of 68 tissue microarray cores of fibroblastic tumors, including intermediate dermatofibrosarcoma protuberans and malignant myxofibrosarcoma and adult-type fibrosarcoma, was used to determine the expression of PD1, PDL1 and TIM3, as well as their relationship with the accumulation of tumor-infiltrating T lymphocytes (TILs).
Results:
Both PD1 and PDL1 expression was only observed in a small proportion of fibroblastic tumors, whereas TIM3 was expressed in almost all tumors. However, only the positive expression of PDL1 was related to tumors with high grade and staging. A considerable number of TILs, including CD4- and CD8A-positive T cells and a small group of FoxP3-positive T cells, was also observed in most tumors. The density of TIM3 was positively correlated with that of TILs. Furthermore, higher densities of TIM3, CD4, CD8A and FoxP3 were observed in PD1 and PDL1 double-positive fibroblastic tumors.
Conclusions:
This study indicates that TILs with high expression of TIM3 may contribute to immunosuppression in the tumor microenvironment of fibroblastic tumors. Patients with fibroblastic tumors with high expression of PD1/PDL1 and TIM3 may therefore benefit from combination therapy with PD1/PDL1 and TIM3 inhibitors.
Insights
Fibroblastic tumors show high TIM3 expression, suggesting a role in immune suppression. Combination therapy targeting PD1/PDL1 and TIM3 may benefit patients with these tumors.
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- Combined therapy targeting T cell immunoglobulin domain and mucin domain 3 (TIM3) and programmed cell death 1/programmed death-ligand 1 (PD1/PDL1) shows promise in solid tumors.
- Expression patterns of PD1/PDL1 and TIM3 in fibroblastic tumors are not well-defined, limiting treatment applications.
Purpose of the Study:
- To investigate the expression of PD1, PDL1, and TIM3 in fibroblastic tumors.
- To determine the relationship between PD1, PDL1, and TIM3 expression and tumor-infiltrating T lymphocytes (TILs).
Main Methods:
- Immunostaining of 68 fibroblastic tumor tissue microarray cores.
- Analysis included intermediate dermatofibrosarcoma protuberans, malignant myxofibrosarcoma, and adult-type fibrosarcoma.
- Assessed PD1, PDL1, TIM3 expression and TILs (CD4, CD8A, FoxP3).
Main Results:
- TIM3 was expressed in nearly all tumors; PD1 and PDL1 were found in a small subset.
- PDL1 expression correlated with high tumor grade and stage.
- TIM3 density positively correlated with TIL density; higher TIM3, CD4, CD8A, and FoxP3 densities were seen in PD1/PDL1 double-positive tumors.
Conclusions:
- High TIM3 expression on TILs may drive immunosuppression in fibroblastic tumors.
- Fibroblastic tumors with high PD1/PDL1 and TIM3 expression could benefit from combined PD1/PDL1 and TIM3 inhibition therapy.
