What question did this study set out to answer?

To examine the roles of perforin and granulysin in the cytotoxic responses of patients with colorectal cancer.

April 22, 2026Open Access

Perforin and Granulysin-Mediated Cytotoxicity in Colorectal Cancer Patients

Key Points

To examine the roles of perforin and granulysin in the cytotoxic responses of patients with colorectal cancer.
Flow cytometry was used to analyze perforin and GNLY-mediated cytotoxicity in peripheral blood.
Cells were labeled with monoclonal antibodies against perforin, GNLY, and various lymphocyte surface antigens.
Intracellular and surface immunofluorescence assessed lymphocyte subpopulation phenotypes and protein expression.
Lower expressions of perforin and GNLY were found in peripheral blood mononuclear cells compared to controls.
Significant reductions in the expression of these proteins correlated with tumor progression stages.
Markedly diminished perforin and GNLY in NK and NKT cells indicated a reduced ability to eliminate tumors.

Abstract

Background and Objectives: The incidence of colorectal cancer (CRC) in developed Western countries is constantly growing. CRC represents the third most common cancer and the second leading cancer-related cause of death worldwide. Innate and adaptive immunity play a pivotal role in the tumor response, but many of these interactions are still not well understood. Granulysin (GNLY) is an effector, cytolytic molecule, present in human cytotoxic granules of different lymphocyte subpopulations, mainly in cytotoxic T cells and NK cells. Pore-forming proteins GNLY, perforin and granzymes play a key role in cell-mediated immune responses against tumors and infections. Materials and Methods: We aimed to analyze perforin and GNLY-mediated cytotoxicity in the peripheral blood of patients with CRC by flow cytometry. Simultaneously, the cells were labeled with monoclonal antibodies against perforin, GNLY and different surface antigens (CD3, CD4, CD8 and CD56). Phenotypes of lymphocyte subpopulation and expression of perforin and GNLY were analyzed using intracellular and surface immunofluorescence. Results: Total perforin and GNLY expressions in peripheral blood mononuclear cells (PBMC) were significantly lower than in the control group. Statistically significant differences were observed in the distribution of perforin and GNLY expression in different stages of tumors classified according to Dukes’, indicating that the percentage of total perforin and GNLY was significantly diminished in accordance with tumor progression. Perforin and GNLY expression were significantly reduced in NK and NKT cells, accompanied by reduced cytolytic potential in patients with CRC and a consequent reduction in their ability to eliminate tumors and infected cells. Conclusions: The determination of cytotoxic potential may provide a valuable assessment of a patient’s immune status and represent a novel therapeutic target. Patients with CRC exhibit markedly impaired perforin- and GNLY-mediated cytotoxicity that correlates with disease progression. Assessment and restoration of cytolytic potential may therefore serve as indicators of immune competence and promising therapeutic strategies to improve perioperative and oncologic outcomes.

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Letica et al. (Mon,) studied this question.

synapsesocial.com/papers/69e865d76e0dea528ddea4c3 https://doi.org/https://doi.org/10.3390/medicina62040791

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