Figure 2.

Myeloid cells are required for the benefic action of HC to chemotherapy in a fibrosarcoma tumor model. Experimental schedule of the implantation and treatment of syngeneic subcutaneous fibrosarcoma in C57Bl/6 mice (a) When tumors reached ~20 mm³, mice were randomly assigned to the different treatment groups. Treatments consisted of the administration of (i) PBS + isotype control antibody (untreated control mice), (ii) chemotherapy + isotype control antibody, (iii) chemotherapy + HC + isotype control antibody, (iv) PBS + anti-CD11b, (v) chemotherapy + anti-CD11b, (vi) chemotherapy + HC + anti-CD11b. The CRM HC was ingested through drinking water from day −1 to 45. Chemotherapy consisted of one injection of the anthracycline MTX at day 0 (or PBS in untreated controls). CD11b-neutralizing antibodies and isotype controls were injected at day −1, 0, 3, 6, 8, 10, 13 and 15. Mean (b) and individual (c,d) tumor growth curves of the treatment groups without CD11b neutralization. Mean (e) and individual (f,g) tumor growth curves of the treatment groups with CD11b neutralization. Of note, mean tumor growth curves in the panels B and E (n = 9/group) were interrupted when more than 50% of the group had reached endpoint. Dot plot (h) illustrating the size of each individual tumor at day 25 post-chemotherapy. Mean ± SD is displayed. Kaplan-Meier survival curves (i,j). ****p< .0001, **p< .01, *p< .05 (comparisons with PBS or explicitly denoted by a segment); ^#p< .05 (comparison between MTX + HC and MTX). For a detailed account of all comparisons, see Supplemental Table 2. CRM, caloric restriction mimetic; HC, hydroxycitrate; i.p., intraperitoneal; MTX, mitoxantrone; PBS, phosphate-buffered saline; s.c., subcutaneous.