Impact of Photothermal Therapy on Tumor Microenvironment and Immune cell Reprogramming

*Corresponding author: (e-mail: [e-mail]).

Abstract

Background: Despite promising preclinical outcomes, translating photothermal therapy (PTT) into clinics needs addressing specific challenges. Our group focuses on enhancing the efficacy of PTT by combining hyperthermia with an adjuvant therapy to level up PTT into clinical use. We studied the immune reprogramming events in vitro and in vivo after treatment.

Methods: PTT was performed on a syngeneic orthotopic breast cancer model in BALB/c mice. Posttreatment, tumors were collected at various time points for immunohistochemistry analysis. Mouse macrophage (RAW 264.7) was exposed to conditioned media collected from PTT-treated and untreated 4T1 cells to assess in vitro macrophage polarization via immunofluorescence and qPCR.

Results: Following treatment, tumor reduction was observed and the tumor microenvironment transitioned toward an antitumorigenic state within 24 hours. A gradual increase in CD68+ve M1 macrophages reflected a pro-inflammatory response, alongside a reduction in CD206+ve M2 macrophages, indicating a decline of an immunosuppressive milieu. Increased spatio-temporal infiltration of macrophages was observed near the treated area. Macrophages exposed to cancer cell-conditioned media exhibited elevated M1 marker expression, while PTT-treated conditioned media favored M2 marker expression. These data were co-related at the mRNA levels as well. Increased levels of phosphorylated STAT1 co-related with the pro-inflammatory status of the cells treated with cancer cell-conditioned media.

Conclusion: After PTT treatment, these observations hint at the potential modulation of the tumor microenvironment for an antitumor immune response. Moreover, the treatment induces reprogramming of macrophages by targeting specific underlying mechanisms, necessitating a more in-depth comprehension.

Publication History

Article published online:
08 July 2024