Temozolomide-induced cytotoxic mechanisms in gamma-delta T cells

Temozolomide-induced cytotoxic mechanisms in gamma-delta T cells refers to the biological process by which the chemotherapy drug temozolomide (TMZ) causes the depletion of gamma-delta (γδ) T cells. TMZ is an alkylating agent used to treat glioblastoma that functions by methylating DNA, primarily at the O6 position of guanine (Friedman et al., 2000) [1]. In γδ T cells, these lesions often trigger the mismatch repair (MMR) pathway, resulting in double-strand breaks and subsequent apoptosis (Lamb et al., 2006) [2]. This interaction is clinically significant because γδ T cells are critical components of the innate-like immune response against tumors and are targets for novel immunotherapies. TMZ-induced lymphopenia can therefore reduce the efficacy of both endogenous and adoptively transferred γδ T cells (Kotecha et al., 2018) [3]. Understanding these mechanisms allows for the optimization of treatment regimens to balance chemotherapy and immunotherapy. Recent advances include the genetic engineering of γδ T cells to express MGMT, making them resistant to TMZ-induced cytotoxicity (Nabors et al., 2021) [4].

Other names

Temozolomide-mediated immunotoxicityTMZ-induced lymphopenia in gamma-delta T cellsTMZ-induced gamma-delta T cell apoptosis

Temozolomide is a DNA-alkylating agent that methylates the O6 position of guanine; in gamma-delta T cells, these lesions trigger the mismatch repair (MMR) system, leading to double-strand breaks and apoptosis (Friedman et al., 2000; Lamb et al., 2006) [1][2].