Date of Graduation

5-2018

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Muldoon, Timothy J.

Abstract

Colorectal Carcinoma (CRC) is one of the deadliest cancers in the world, with 150,000 new cases annually in the United States. Traditional treatments include chemotherapy and invasive surgery; however, research has shown that only 25% of patients that undergo traditional treatment have a positive result. Immunotherapy is an emerging form of cancer treatment that utilizes the patients’immune system to fight cancer cells by targeting inflammation, which plays a large role in the proliferation and metastasis of cancer cells.

Tumor-associated macrophages (TAMs) are immune cells that affect the inflammatory microenvironment of tumors. TAMs are M1 in the early stages of tumors, and are phagocytic and cytotoxic. However, these macrophages shift towards M2 as the tumors grow, which promote tumorigenesis, angiogenesis, and immunosuppression in CRC. M2 macrophage density may indicate the pro-tumor effects of TAMs, and it is expected that fewer M2 macrophages is correlated with a higher survival rate of patients with cancer.

The central hypothesis in this study is that blockade of TAM recruitment via immunotherapy would decrease M2 macrophages in the tumor microenvironment, resulting in a more treatable tumor. Monocyte chemoattractant protein-1 (CCL-2) is a cytokine secreted by tumors known to recruit monocytes that differentiate into TAMs. In our study, we examined the effects of CCL-2 blockade in a murine allograft model of CRC.

Thirty 10-week old Balb/c mice were injected subcutaneously with 1x105 CT26 murine colon carcinoma cells. Fifteen mice received anti-CCL-2 immunotherapy, and 15 control mice received saline. Tumor allografts grew until they reached 75 mm3. Tumor sections were stained for M2 macrophages and total cells, and then imaged to determine the M2 macrophage density. On Day10, the tumors were 13.02 +/- 3.04 and 11.03 +/- 3.99 times their original sizes, and M2 macrophage densities were 593.3 +/- 9.0 and 559.2 +/- 7.0 M2 macrophages/mm2 for the control and treated mice respectively.

Keywords

Immunotherapy; Colon Cancer; Antibody; Cellular Imaging

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