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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. 

As a result of millions of years of transposon activity, multiple rounds of ancient polyploidization, and large populations that preserve diversity, maize has an extremely structurally diverse genome, evidenced by high-quality genome assemblies that capture substantial levels of both tropical and temperate diversity. We generated a pangenome representation (the Practical Haplotype Graph, PHG) of these assemblies in a database, representing the pangenome haplotype diversity and providing an initial estimate of structural diversity. We leveraged the pangenome to accurately impute haplotypes and genotypes of taxa using various kinds of sequence data, ranging from WGS to extremely-low coverage GBS. We imputed the genotypes of the recombinant inbred lines of the NAM population with over 99% mean accuracy, while unrelated germplasm attained a mean imputation accuracy of 92 or 95% when using GBS or WGS data, respectively. Most of the imputation errors occur in haplotypes within European or tropical germplasm, which have yet to be represented in the maize PHG database. Also, the PHG stores the imputation data in a 30,000-fold more space-efficient manner than a standard genotype file, which is a key improvement when dealing with large scale data.