An emerging strategy called immunomodulation therapy, or immunotherapy, has gained clinical momentum in recent years to aid neoadjuvant CRT in reducing tumor burden and recurrence risk. Thus, the development of more effective treatments for CRC is in urgent need. However, pCR is achieved in less than 30% of cases, resulting in distal recurrence rates of 25%, which is the primary cause of CRC-related death. Patients achieving pCR have a reduced risk of distal recurrence. Ideally, patients will exhibit pathologic complete response (pCR) when there is an absence of residual cancer cells in a histological examination. Following neoadjuvant CRT, biopsies are examined to determine pathologic response. The standard of treatment for locally-advanced CRC is neoadjuvant chemoradiotherapy (CRT) using 5-fluorouracil (5-FU), followed by total mesorectal excision (TME) surgery. Locally-advanced CRC (stages II-III), which accounts for approximately 20% of cases, describes cancer that has spread from the site of the primary tumor to surrounding tissue or lymph nodes but has not metastasized. The findings in this work suggest that the blockade of CCL2 is sufficient in the reduction of TAMs that are recruited into the tumor microenvironment and has the ability to modestly alter tumor perfusion during early-tumor response to treatment even though the overall benefit is relatively modest.Ĭolorectal cancer (CRC) is estimated to account for 149,500 new cancer cases annually in the United States, making it the 4 th most common cancer type overall (behind breast, prostate, and lung), and resulting in 52,980 annual deaths.
Modest improvements in oxygen saturation (~ 30%) were observed in the combination group. This shows that the addition of anti-CCL2 to 5-FU slowed the fold-change (change from the original measurement to the final measurement) in tumor volume from Day 0 to Day 12 (~ 5 fold). A subcutaneous tumor model using Balb/c mice injected with CT26 colon carcinoma cells received either a saline or isotype control, anti-CCL2, 5-FU, or a combination of anti-CCL2 and 5-FU.įindings show that 12 days post-treatment, monocyte recruitment was significantly reduced by approximately 61% in the combination group. It was hypothesized that the blockade of TAMs will alter tumor perfusion, increasing chemotherapy response. In this study, we examine whether blockade of monocyte recruitment via CCL2 (macrophage chemoattractant protein-1) leads to enhanced sensitivity of 5-fluorouracil (5-FU) in a CT26-Balb/c mouse model of CRC. Changes in vascularization can be non-invasively assessed via diffuse reflectance spectroscopy using hemoglobin concentrations and oxygenation in a localized tumor volume. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macrophages (TAMs) and promote tumor angiogenesis. Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis.
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