Functional plasticity of neutrophils after low- or high-dose irradiation in cancer treatment – A mini review

Abstract

Over the last several decades, radiotherapy has been considered the primary treatment option for a broad range of cancer types, aimed at prolonging patients’ survival and slowing down tumor regression. However, therapeutic outcomes of radiotherapy remain limited, and patients suffer from relapse shortly after radiation. Neutrophils can initiate an immune response to infection by releasing cytokines and chemokines to actively combat pathogens. In tumor immune microenvironment, tumor-derived signals reprogram neutrophils and induce their heterogeneity and functional versatility to promote or inhibit tumor growth. In this review, we present an overview of the typical phenotypes of neutrophils that emerge after exposure to low- and high-dose radiation. These phenotypes hold potential for developing synergistic therapeutic strategies to inhibit immunosuppressive activity and improve the antitumor effects of neutrophils to render radiation therapy as a more effective strategy for cancer patients, through tumor microenvironment modulation.

β-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers

“…There were reports suggesting that fractionated radiotherapy polarizes newly recruited neutrophils toward the antitumor N1 phenotype in the TME. 62 , 63 Our findings demonstrate that, similar to fractionated radiotherapy, the NQO1 bioactivatable drug β-Lap induces tumor-selective killing by polarizing tumor-infiltrated neutrophils into the antitumor N1 type.…”

“…It is noteworthy that low-dose and high-dose radiation have different effects on neutrophil polarization; understanding these differences may inform synergistic therapeutic strategies to enhance radiation therapy. 63 Furthermore, the antitumor subpopulation of neutrophils synergizes with PD-L1-based immunotherapy in a murine lung cancer model, modulating the protumor/antitumor neutrophil ratio and enhancing the antitumor function of a specific subset of neutrophils, and promotes T cell proliferation. 26 Understanding the plasticity and diversity of tumor-infiltrating or tumor-associated neutrophils is beneficial for assessing therapeutic efficacy.…”

Chemotherapy-induced toxic epidermal necrolysis in a patient with multiple myeloma, a case report and literature review

“…Similarly, Toxic Epidermal Necrolysis (TEN), more than 30% of the skin surface involved in erosion of mucosae, occurs in a variety of diseases and shares similar symptoms with SJS (1)(2)(3)(4)(5). Both conditions represent severe drug-induced skin reactions that can be mediated by the immune response and have a high mortality rate observed in affected patients (6,7).…”