Wan FatinAmiraWan Mohd Zawawi, M. H. Hibma, M. I. Salim & K. Jemon
ABSTRACT
Breast cancer is the most common cancer that causes death in women. Conventional therapies, including surgery and chemotherapy, have diferent therapeutic efects and are commonly associated with risks and side efects. Near infrared radiation is a technique with few side efects that is used for local hyperthermia, typically as an adjuvant to other cancer therapies. The understanding of the use of near NIR as a monotherapy, and its efects on the immune cells activation and infltration, are limited. In this study, we investigate the efects of HT treatment using NIR on tumor regression and on the immune cells and molecules in breast tumors. Results from this study demonstrated that local HT by NIR at 43 °C reduced tumor progression and signifcantly increased the median survival of tumor-bearing mice. Immunohistochemical analysis revealed a signifcant reduction in cells proliferation in treated tumor, which was accompanied by an abundance of heat shock protein 70 (Hsp70). Increased numbers of activated dendritic cells were observed in the draining lymph nodes of the mice, along with infltration of T cells, NK cells and B cells into the tumor. In contrast, tumor-infltrated regulatory T cells were largely diminished from the tumor. In addition, higher IFN-γ and IL-2 secretion was observed in tumor of treated mice. Overall, results from this present study extends the understanding of using local HT by NIR to stimulate a favourable immune response against breast cancer.
INTRODUCTION
Breast cancer is the most common cancer among women, regardless race or ethnicity. Te number of new cases increases each year with the growing of population. A variety of treatments that are available, however almost all conventional treatments, including chemotherapy and surgery, come with side effects. Hyperthermia (HT) which one of many cancer treatments available, is a therapy that uses heat to increase body temperature above the normal temperature. Tis could be achieved either systemically, or locally at a particular area of the body. As a non-invasive cancer treatment strategy, local HT is ideally suitable to treat superficial tumors such as neck or breast tumors, where the temperature given is readily attainable and tolerable to patients. Local HT can be either within the range of 39–48 °C or exceed temperature around 70–90 °C, at which different temperature could give different effects to the tumor and the adjacent normal tissues. The main objective of local moderate HT is to kill, weaken, or sensitize the cancer cells as well as to improve the anti-tumor immunity, without affecting the surrounding normal tissues. Besides inhibiting tumor growth by necrosis and apoptosis, multiple cancer-related studies have reported the application of fever-range HT as an immunotherapeutic agent. HT was reported to stimulate the activation of antigen presenting cells (APCs) by releasing the heat shock protein (Hsp) from the dying heat-stressed cancer cells. In addition, these dying cells also produce exosomes that assist the maturation of APCs and increasing tumor-specific cytotoxic T lymphocyte (CTL) response. High level of lymphocytes was also observed in lymph node of mice treated with HT, implying the augmentation of immune response by HT treatment. Local HT applied at 40–43 °C also facilitates immune cells trafficking towards tumor by increasing the permeability of tumor vasculature and perfusion. Furthermore, electro-HT provides favorable tumor microenvironment (TME) for immune cells to function optimally, hence would be beneficial for combination with immunotherapy.