Frequency determination of breast tumor-reactive CD4 and CD8 T cells in humans: unveiling the antitumor immune response

Author(s)

Pinho, Mariana Pereira ^[1] ; Patente, Thiago Andrade ^[1] ; Flatow, Elizabeth Alexandra ^[1] ; Sallusto, Federica ^{[2, 3]} ; Marzagao Barbuto, Jose Alexandre ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Ave Prof Lineu Prestes, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Svizzera Italiana, Fac Biomed Sci, Inst Res Biomed, Bellinzona - Switzerland

^[3] Swiss Fed Inst Technol, Inst Microbiol, Zurich - Switzerland

• Document type: Journal article
• Source: ONCOIMMUNOLOGY; v. 8, n. 8 MAY 2019.
• Web of Science Citations: 0

Abstract

As cancer immunotherapy gains importance, the determination of a patient's ability to react to his/her tumor is unquestionably relevant. Though the presence of T cells that recognize specific tumor antigens is well established, the total frequency of tumor-reactive T cells in humans is difficult to assess, especially due to the lack of broad analysis techniques. Here, we describe a strategy that allows this determination, in both CD4 and CD8 compartments, using T cell proliferation induced by tumor cell-lysate pulsed dendritic cells as the readout. All 12 healthy donor tested had circulating CD4 and CD8 tumor cell-reactive T cells. The detection of these T cells, not only in the naive but also in the memory compartment, can be seen as an evidence of tumor immunosurveillance in humans. As expected, breast cancer patients had higher frequencies of blood tumor-reactive T cells, but with differences among breast cancer subtypes. Interestingly, the frequency of blood tumor-reactive T cells in patients did not correlate to the frequency of infiltrating tumor-reactive T cells, highlighting the danger of implying a local tumor response from blood obtained data. In conclusion, these data add T cell evidence to immunosurveillance in humans, confirm that immune parameters in blood may be misleading and describe a tool to follow the tumor-specific immune response in patients and, thus, to design better immunotherapeutic approaches. (AU)

• FAPESP's process: 14/25988-1 - Analysis of the T cell repertoire in cancer patients: unveiling the antitumor immune response in humans
• Grantee: Mariana Pereira Pinho
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/01137-8 - Analysis of the tumor-antigen specific T cell repertoire in healthy donors using T cell libraries
• Grantee: Mariana Pereira Pinho
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate