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Spontaneous class-switched antibody responses at endometrial cancer tumor bed drives superior patients’ outcome

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MANDAL, G; Biswas, S; Anadon, CM; Yu, X; Gatenbee, CD; Prabhakaran, S; Payne, KK; Chaurio, RA; Martin, A; Innamarato, P; Moran, C; Powers, JJ ...
Published in: The Journal of Immunology
May 1, 2022

The role of humoral responses in endometrial cancer remains insufficiently investigated. Using a cohort of 107 patients with different histological subtypes of endometrial carcinoma, we report that concomitant accumulation of T, B and plasma cells at tumor beds predicts better survival. However, only B cell markers predict survival specifically in high-grade endometrioid type and serous tumors. Accordingly, immune protection is associated with class-switched IgA and, to a lesser extent, IgG. Notably, expression of polymeric immunoglobulin receptor (pIgR) by tumor cells and its occupancy by IgA are superior predictors of outcome, and correlate with defects in methyl mismatch repair. Mechanistically, pIgR-dependent, antigen-independent IgA occupancy drives inflammatory pathways associated with IFN and TNF signaling in tumor cells, along with apoptotic and ER stress pathways, while thwarting DNA repair mechanisms. Therefore, coordinated humoral and cellular immune responses, characterized by IgA:pIgR interactions in tumor cells, determine the progression of human endometrial cancer, and therefore the potential for effective immunotherapies.Supported by grants from NIH (R01CA157664, R01CA124515, R01CA178687 and R01CA211913), and from Cancer Center Support Grant (CCSG) CA076292

Duke Scholars

Published In

The Journal of Immunology

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

May 1, 2022

Volume

208

Issue

1_Supplement

Start / End Page

177.01 / 177.01

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Immunology
  • 3204 Immunology
  • 3101 Biochemistry and cell biology
  • 1107 Immunology
 

Citation

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MANDAL, G., Biswas, S., Anadon, C. M., Yu, X., Gatenbee, C. D., Prabhakaran, S., … Conejo-Garcia, J. R. (2022). Spontaneous class-switched antibody responses at endometrial cancer tumor bed drives superior patients’ outcome. In The Journal of Immunology (Vol. 208, pp. 177.01-177.01). Oxford University Press (OUP). https://doi.org/10.4049/jimmunol.208.supp.177.01
MANDAL, G. U. N. J. A. N., Subir Biswas, Carmen M. Anadon, Xiaoqing Yu, Chandler D. Gatenbee, Sandhya Prabhakaran, Kyle K. Payne, et al. “Spontaneous class-switched antibody responses at endometrial cancer tumor bed drives superior patients’ outcome.” In The Journal of Immunology, 208:177.01-177.01. Oxford University Press (OUP), 2022. https://doi.org/10.4049/jimmunol.208.supp.177.01.
MANDAL G, Biswas S, Anadon CM, Yu X, Gatenbee CD, Prabhakaran S, et al. Spontaneous class-switched antibody responses at endometrial cancer tumor bed drives superior patients’ outcome. In: The Journal of Immunology. Oxford University Press (OUP); 2022. p. 177.01-177.01.
MANDAL, G. U. N. J. A. N., et al. “Spontaneous class-switched antibody responses at endometrial cancer tumor bed drives superior patients’ outcome.” The Journal of Immunology, vol. 208, no. 1_Supplement, Oxford University Press (OUP), 2022, pp. 177.01-177.01. Crossref, doi:10.4049/jimmunol.208.supp.177.01.
MANDAL G, Biswas S, Anadon CM, Yu X, Gatenbee CD, Prabhakaran S, Payne KK, Chaurio RA, Martin A, Innamarato P, Moran C, Powers JJ, Harro CM, Mine JA, Sprenger KB, Rigolizzo KE, Wang X, Curiel TJ, Rodriguez PC, Anderson ARA, Saglam O, Conejo-Garcia JR. Spontaneous class-switched antibody responses at endometrial cancer tumor bed drives superior patients’ outcome. The Journal of Immunology. Oxford University Press (OUP); 2022. p. 177.01-177.01.

Published In

The Journal of Immunology

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

May 1, 2022

Volume

208

Issue

1_Supplement

Start / End Page

177.01 / 177.01

Publisher

Oxford University Press (OUP)

Related Subject Headings

  • Immunology
  • 3204 Immunology
  • 3101 Biochemistry and cell biology
  • 1107 Immunology