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2099-12-31
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SYSTEMIC IMMUNE MEDIATORS REFLECT TUMOR-INFILTRATING LYMPHOCYTE INTENSITY AND PREDICT THERAPEUTIC RESPONSE IN TRIPLE-NEGATIVE BREAST CÂNCER
Author
Lopes, Ananda D
Galdino, Nayane A L
Figueiredo, Amanda B
Brianese, Rafael C
Morais, Katia L P
Brot, Marina De
Osório, Cynthia A B T
Carvalho, Andrea Teixeira de
Calsavara, Vinicius F
Evangelista, Guilherme F B
Alves, Natalia S
Makdissi, Fabiana B
Sanches, Solange M
Lima, Vladmir C Cordeiro de
Carraro, Dirce M
Gollob, Kenneth J
Galdino, Nayane A L
Figueiredo, Amanda B
Brianese, Rafael C
Morais, Katia L P
Brot, Marina De
Osório, Cynthia A B T
Carvalho, Andrea Teixeira de
Calsavara, Vinicius F
Evangelista, Guilherme F B
Alves, Natalia S
Makdissi, Fabiana B
Sanches, Solange M
Lima, Vladmir C Cordeiro de
Carraro, Dirce M
Gollob, Kenneth J
Affilliation
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Laboratory of Genomics and Molecular Biology. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Pathology. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil/Laboratory of Genomics and Molecular Biology. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil/Department of Pathology. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Laboratory of Epidemiology and Statistics. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Mastology. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Clinical Oncology. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Clinical Oncology. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Laboratory of Genomics and Molecular Biology. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil/INCT-INCITO, São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil./ Translational Immuno-oncology Laboratory. Hospital Israelita Albert Einstein. São Paulo, SP, Brazil/Center for Research in Immuno-oncology. Hospital Israelita Albert Einstein. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Laboratory of Genomics and Molecular Biology. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Pathology. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil/Laboratory of Genomics and Molecular Biology. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil/Department of Pathology. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Laboratory of Epidemiology and Statistics. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Mastology. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Clinical Oncology. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Department of Clinical Oncology. A.C.Camargo Cancer Center. São Paulo, SP, Brazil.
Laboratory of Genomics and Molecular Biology. International Research Center. A.C. Camargo Cancer Center. São Paulo, SP, Brazil/INCT-INCITO, São Paulo, SP, Brazil.
Translational Immuno-oncology Group. International Research Center. A.C.Camargo Cancer Center. São Paulo, SP, Brazil./ Translational Immuno-oncology Laboratory. Hospital Israelita Albert Einstein. São Paulo, SP, Brazil/Center for Research in Immuno-oncology. Hospital Israelita Albert Einstein. São Paulo, SP, Brazil.
Abstract
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumor-infiltrating lymphocytes (TILs) in pre-treated tumor tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders vs. non-pCR, with AUC values of 0.64 - 0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72 - 0.82). Lastly, performing a progression free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long and short survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival.
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