Fig. 6: PIGR-mediated IgA transcytosis promotes anti-tumor activity in vivo.

A–D Experimental schematic (A), tumor growth curves (B), tumor weight (C), and tumor images (D) of C57BL/6 wild-type mice subcutaneously inoculated with control- or PIGR-overexpressing MC38 cells. Anti-CD20 antibodies (250 μg per mouse) were administered at the time of tumor cell implantation and at 10-day intervals to deplete B cells (n = 4 independent experiments). *P = 0.0271 and **P = 0.0057 in (B), *P = 0.0195 and **P = 0.0093 in (C). E, F ELISA quantification of intra-tumor IgG (E) and IgA (F) levels from panel (D). n = 4 independent experiments (****P < 0.0001). G–J Schematic of experimental design (G), tumor growth curves (H), tumor images (I) and tumor weight (J) in WT (IgA^+/+) and IgA-deficient (IgA^-/-) mice inoculated subcutaneously with control- and PIGR- overexpressing MC38 cells (n = 5 independent experiments). *P = 0.0110 and **P = 0.0063 in (H), *P = 0.0205 (between Control (IgA^+/+) and PIGR (IgA^+/+)) and **P = 0.0115 (between PIGR (IgA^+/+) and PIGR (IgA^-/-)) in (J). K–M Quantification of tumor infiltrating IFNγ⁺CD8⁺ T cells (K), TNFα⁺CD8⁺ T cells (L) and GZMB⁺CD8⁺ T cells (M) from panel (I). n = 5 independent experiments, *P = 0.0160 in (K), *P = 0.0362 (between Control (IgA^+/+) and PIGR (IgA^+/+)) and **P = 0.0484 (between PIGR (IgA^+/+) and PIGR (IgA^-/-)) in (L), *P = 0.0254 in (M). N Pie chart showing the classification of 85 PSCC patients according to the IHC scores for PIGR and IgA in PSCC tumor sections. High expression groups: IHC score ≥ 3. Low expression groups: IHC score ≤ 2. O Kaplan-Meier survival curve for PSCC patients grouped by high or low co-expression of PIGR and IGA based on IHC scores (*P = 0.0382). P–R Correlation between overall survival and the transcripts of PIGR and IgA in patients from the TCGA database for CESC (**P = 0.0044) (P), HNSCC (*P = 0.0410) Q and CDAD (*P = 0.0303) (R). CESC: Cervical squamous cell carcinoma, HNSCC: Head and neck squamous cell carcinoma, COAD: Colon adenocarcinoma. A two-sided unpaired Student’s t test was used in (C), (E), (F), (J–M). A two-way ANOVA test was used in (B) and (H). Two-sided log-rank (Mantel–Cox) test was used in (O–R). Data are presented as mean ± s.e.m. ns: not significant (P > 0.05). Figures (A and G) were created in BioRender. Pan, W. (2025) https://biorender.com/udc23v6. Source data are provided as a Source Data file.