FOXP3+ Cells Recruited by CCL22 into Breast Cancer Correlates with Less Tumor Nodal Infiltration.
BACKGROUND
Regulatory T-cells (Tregs) are a T-cell subpopulation with suppressive capacities, which are specifically attracted by C-C motif chemokine 22 (CCL22). Treg infiltration of tumors is associated with a poor prognosis in many patients. We aimed to investigate whether CCL22 is expressed in human breast cancer and whether its presence is associated with Treg infiltration.


METHODS
Eighty paraffin-embedded human breast cancer samples were stained for CCL22 and for the Treg-specific transcription factor forkhead box P3 (FOXP3). Expression was evaluated in a semi-quantitative manner.


RESULTS
FOXP3(+) cells infiltrated 50% of the breast tumors. Moreover, Treg infiltrated 93% of the tertiary lymphoid structures. CCL22 expression positively correlated with FOXP3(+) cell infiltration into the tertiary lymphoid structures.


CONCLUSIONS
Our results demonstrate that CCL22 expression correlates with infiltration by FOXP3(+) cells. Interestingly, Treg presence negatively correlated with positive nodal status. In addition to their unfavorable role as mediators of evasion from antitumor immune response, Tregs might also have a beneficial role by reducing inflammation thereby limiting early tumor growth and spreading.
Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany Department of Clinical Pharmacology, Ludwig Maximilians University of Munich, Munich, Germany.
Christoph P
CP
Freier
Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany.
Christina
C
Kuhn
Department of Clinical Pharmacology, Ludwig Maximilians University of Munich, Munich, Germany.
Stefan
S
Endres
Department of Pathology, Ludwig Maximilians University of Munich, Munich, Germany.
Doris
D
Mayr
Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany.
Klaus
K
Friese
Department of Obstetrics and Gynecology, Ludwig Maximilians University of Munich, Munich, Germany udo.jeschke@med.uni-muenchen.de.
Udo
U
Jeschke
Department of Clinical Pharmacology, Ludwig Maximilians University of Munich, Munich, Germany.
David
D
Anz
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D054422:Chemokine CCL22 / Q000502:physiology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D007113:Immunity, Innate; D008198:Lymph Nodes / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
C515482:CCL22 protein, human; D054422:Chemokine CCL22; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
CCL22; FOXP3; Regulatory T-cells; breast cancer; immunohistochemistry; tertiary lymphoid structures