Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy
Abstract Background Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macro...
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| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-022-00493-5 |
| _version_ | 1828400006848053248 |
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| author | Shelby N. Bess Gage J. Greening Narasimhan Rajaram Timothy J. Muldoon |
| author_facet | Shelby N. Bess Gage J. Greening Narasimhan Rajaram Timothy J. Muldoon |
| author_sort | Shelby N. Bess |
| collection | DOAJ |
| description | Abstract Background Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macrophages (TAMs) and promote tumor angiogenesis. Changes in vascularization can be non-invasively assessed via diffuse reflectance spectroscopy using hemoglobin concentrations and oxygenation in a localized tumor volume. 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. It was hypothesized that the blockade of TAMs will alter tumor perfusion, increasing chemotherapy response. 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. Results Findings show that 12 days post-treatment, monocyte recruitment was significantly reduced by approximately 61% 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). Modest improvements in oxygen saturation (~ 30%) were observed in the combination group. Conclusion 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. |
| first_indexed | 2024-12-10T09:24:57Z |
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| id | doaj.art-b4795f8985c64b92b7e0c5d09c1762e7 |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-10T09:24:57Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-b4795f8985c64b92b7e0c5d09c1762e72022-12-22T01:54:34ZengBMCBMC Immunology1471-21722022-04-0123111410.1186/s12865-022-00493-5Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopyShelby N. Bess0Gage J. Greening1Narasimhan Rajaram2Timothy J. Muldoon3Department of Biomedical Engineering, University of Arkansas, 1 University of ArkansasDepartment of Biomedical Engineering, University of Arkansas, 1 University of ArkansasDepartment of Biomedical Engineering, University of Arkansas, 1 University of ArkansasDepartment of Biomedical Engineering, University of Arkansas, 1 University of ArkansasAbstract Background Immunotherapy in colorectal cancer (CRC) regulates specific immune checkpoints and, when used in combination with chemotherapy, can improve patient prognosis. One specific immune checkpoint is the recruitment of circulating monocytes that differentiate into tumor-associated macrophages (TAMs) and promote tumor angiogenesis. Changes in vascularization can be non-invasively assessed via diffuse reflectance spectroscopy using hemoglobin concentrations and oxygenation in a localized tumor volume. 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. It was hypothesized that the blockade of TAMs will alter tumor perfusion, increasing chemotherapy response. 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. Results Findings show that 12 days post-treatment, monocyte recruitment was significantly reduced by approximately 61% 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). Modest improvements in oxygen saturation (~ 30%) were observed in the combination group. Conclusion 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.https://doi.org/10.1186/s12865-022-00493-5Colorectal cancerTumor-associated macrophagesDiffuse reflectance spectroscopyImmunomodulation |
| spellingShingle | Shelby N. Bess Gage J. Greening Narasimhan Rajaram Timothy J. Muldoon Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy BMC Immunology Colorectal cancer Tumor-associated macrophages Diffuse reflectance spectroscopy Immunomodulation |
| title | Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy |
| title_full | Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy |
| title_fullStr | Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy |
| title_full_unstemmed | Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy |
| title_short | Macrophage-targeted anti-CCL2 immunotherapy enhances tumor sensitivity to 5-fluorouracil in a Balb/c-CT26 murine colon carcinoma model measured using diffuse reflectance spectroscopy |
| title_sort | macrophage targeted anti ccl2 immunotherapy enhances tumor sensitivity to 5 fluorouracil in a balb c ct26 murine colon carcinoma model measured using diffuse reflectance spectroscopy |
| topic | Colorectal cancer Tumor-associated macrophages Diffuse reflectance spectroscopy Immunomodulation |
| url | https://doi.org/10.1186/s12865-022-00493-5 |
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