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. Author manuscript; available in PMC: 2017 Aug 12.
Published in final edited form as: Sci Transl Med. 2017 Apr 12;9(385):eaak9679. doi: 10.1126/scitranslmed.aak9679

Fig. 7. LTβR-activation is implicated in HEV formation during antiangiogenic immunotherapy.

Fig. 7

(A) Top: Schematic of LTβR effects with agonistic and antagonistic anti-LTβR antibodies. Bottom: Image of an HEV. Scale bar, 50 μm. (B to G) MMTV-PyMT mice were treated as indicated. (B) Number of HEVs per square millimeter of tumor area. IgG, n = 8; D + P, n = 8; D + P + agonistic anti-LTβR (Ag), n = 5; D + P + antagonistic anti-LTβR (Ant), n = 5. (C) Number of CD8+ cells around tumor vessels. IgG, n = 21; D + P, n = 18; D + P + Ag, n = 39; D + P + Ant, n = 18. (D) Number of GzB+CD8+ cells per field. IgG, n = 10; D + P, n = 11; D + P + Ag, n = 13; D + P + Ant, n = 11. (E) Quantitation and visualization of CC3+ apoptotic cells. IgG, n = 25; D + P, n = 20; D + P + Ag, n = 27; D + P + Ant, n = 26. Scale bars, 50 μm. (F) Quantitation and visualization of necrotic areas in MMTV-PyMT tumors. IgG, n = 4; D + P, n = 5; D + P + Ag, n = 5; D + P + Ant, n = 4. Scale bars, 1 mm. (G) Tumor size in PyMT mice under different treatment conditions. IgG, n = 4; D + P, n = 4; D + P + Ag, n = 4. (H) Quantitation and visualization of MECA79+CD31+ tumor vessels in NFpp10-GBM tumors treated as indicated. B + P, n = 10; B + P + Ag, n = 9. Scale bars, 50 μm (low-magnification images); 20 μm (high-magnification images). (I) FACS analysis of GzB+CD3+CD8+ CTLs under the different treatment conditions. IgG, n = 3; Ag, n = 3; B + P, n = 4; B + P + Ag, n = 4. (J) Tumor burden of NFpp10-GBM mice under different treatment conditions. IgG and Ag, n = 3; B + P and B + P + Ag, n = 4. Data are presented as means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 (for exact P values, see table S2); Mann-Whitney test. Black asterisks represent P values for comparisons between IgG and different treatments; red asterisks represent P values for other comparisons.