BMC Cancer (Oct 2018)

PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells?

  • Ramón Cantero-Cid,
  • José Casas-Martin,
  • Enrique Hernández-Jiménez,
  • Carolina Cubillos-Zapata,
  • Aníbal Varela-Serrano,
  • José Avendaño-Ortiz,
  • Marta Casarrubios,
  • Karla Montalbán-Hernández,
  • Ignacio Villacañas-Gil,
  • Laura Guerra-Pastrián,
  • Begoña Peinado,
  • Cristóbal Marcano,
  • Luis A Aguirre,
  • Eduardo López-Collazo

DOI
https://doi.org/10.1186/s12885-018-4853-0
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 9

Abstract

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Abstract Background The analysis of tumour-infiltrating immune cells within patients’ tumour samples in colorectal cancer (CRC) has become an independent predictor of patient survival. The tumour microenvironment and the immune checkpoints, such as PD-L1/PD-1, are relevant to the prognoses and also appear to be relevant for further CRC therapies. Methods We analysed the presence and features of the infiltrated monocyte/macrophage and lymphocyte populations in both tumour and peritumour samples from patients with CRC (n = 15). Results We detected a large number of CD14+ monocytes/macrophages with an alternative phenotype (CD64+CD163+) and CD4+ lymphocytes that infiltrated the tumour, but not the peritumour area. The monocytes/macrophages expressed PD-L1, whereas the lymphocytes were PD-1+; however, we did not find high PD-L1 levels in the tumour cells. Coculture of circulating naïve human monocytes/macrophages and lymphocytes with tumour cells from patients with proficient mismatch repair CRC induced both an alternative phenotype with higher expression of PD-L1 in CD14+ cells and the T-cell exhaustion phenomenon. The addition of an α-PD-1 antibody restored lymphocyte proliferation. Conclusion These results emphasise the interesting nature of immune checkpoint shifting therapies, which have potential clinical applications in the context of colorectal cancer.

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