PANoramic View: The Photography of Pancreatic Cancer and Immune Cells Through the IL-40 Lens
Description
Background: Co-stimulatory and adhesion pathways shape anti-tumor immunity by regulating T-cell activation and trafficking. TNFSF9 (4-1BBL) engages CD137 (4-1BB) to enhance T-cell proliferation and cytotoxicity, while ICAM-1 (CD54) and ICAM-2 (CD102) bind LFA-1 (αLβ2) to stabilize immune synapses. Although well studied in antigen-presenting cells, their tumor-cell expression is variable and cytokine-dependent. Here, we examined how recombinant human interleukin-40 (IL-40) regulates 4-1BBL, ICAM-1, and ICAM-2 in cervical cancer (HeLa) and pancreatic adenocarcinoma (PAN48) cells.
Methods: HeLa and PAN48 cells were treated with IL-40 and subjected to multiple assays to assess cellular responses. Clonogenic survival and quick proliferation assays were performed to evaluate cell growth and viability. RT-PCR was conducted to quantify the expression of the co-stimulatory molecules 4-1BBL, ICAM-1, and ICAM-2. In addition, immunohistochemistry (IHC) was used to further characterize IL-40–mediated regulation of these targets at the protein level.
Results: RT-PCR revealed lineage-dependent IL-40 effects on co-stimulatory/adhesion genes. In HeLa cells, IL-40 downregulated 4-1BBL, ICAM-1, and ICAM-2 across replicates. In PAN48 cells, IL-40 upregulated 4-1BBL and ICAM-2, concomitant with ICAM-1 downregulation. These transcriptional patterns were corroborated at the protein level by IHC, supporting divergent, tumor-origin–specific responses to IL-40.
Conclusion: IL-40 regulates co-stimulatory and adhesion molecules in a cell line–dependent manner. In HeLa cells, IL-40 downregulated 4-1BBL, ICAM-1, and ICAM-2, suggesting immune escape, whereas in pancreatic cells it upregulated 4-1BBL and ICAM-2 with concomitant ICAM-1 loss, suggesting immune activation. Thus, IL-40 acts as a context-dependent modulator of tumor–immune crosstalk with therapeutic potential.
Citation Information
Sheng, Yuting; Mayberry, Trenton; Cowan, Braydon; Marrah, Austin; Wakefield, Mark R.; and Fang, Yujiang, "PANoramic View: The Photography of Pancreatic Cancer and Immune Cells Through the IL-40 Lens" (2026). Office of Research DMU Research Symposium. 74.
https://digitalcommons.dmu.edu/researchsymposium/2025rs/2025abstracts/74
PANoramic View: The Photography of Pancreatic Cancer and Immune Cells Through the IL-40 Lens
Background: Co-stimulatory and adhesion pathways shape anti-tumor immunity by regulating T-cell activation and trafficking. TNFSF9 (4-1BBL) engages CD137 (4-1BB) to enhance T-cell proliferation and cytotoxicity, while ICAM-1 (CD54) and ICAM-2 (CD102) bind LFA-1 (αLβ2) to stabilize immune synapses. Although well studied in antigen-presenting cells, their tumor-cell expression is variable and cytokine-dependent. Here, we examined how recombinant human interleukin-40 (IL-40) regulates 4-1BBL, ICAM-1, and ICAM-2 in cervical cancer (HeLa) and pancreatic adenocarcinoma (PAN48) cells.
Methods: HeLa and PAN48 cells were treated with IL-40 and subjected to multiple assays to assess cellular responses. Clonogenic survival and quick proliferation assays were performed to evaluate cell growth and viability. RT-PCR was conducted to quantify the expression of the co-stimulatory molecules 4-1BBL, ICAM-1, and ICAM-2. In addition, immunohistochemistry (IHC) was used to further characterize IL-40–mediated regulation of these targets at the protein level.
Results: RT-PCR revealed lineage-dependent IL-40 effects on co-stimulatory/adhesion genes. In HeLa cells, IL-40 downregulated 4-1BBL, ICAM-1, and ICAM-2 across replicates. In PAN48 cells, IL-40 upregulated 4-1BBL and ICAM-2, concomitant with ICAM-1 downregulation. These transcriptional patterns were corroborated at the protein level by IHC, supporting divergent, tumor-origin–specific responses to IL-40.
Conclusion: IL-40 regulates co-stimulatory and adhesion molecules in a cell line–dependent manner. In HeLa cells, IL-40 downregulated 4-1BBL, ICAM-1, and ICAM-2, suggesting immune escape, whereas in pancreatic cells it upregulated 4-1BBL and ICAM-2 with concomitant ICAM-1 loss, suggesting immune activation. Thus, IL-40 acts as a context-dependent modulator of tumor–immune crosstalk with therapeutic potential.
