Potential immune priming of the tumor microenvironment with FOLFOX chemotherapy in locally advanced rectal cancer Journal Article
| Authors: | Roxburgh, C. S.; Shia, J.; Vakiani, E.; Daniel, T.; Weiser, M. R. |
| Article Title: | Potential immune priming of the tumor microenvironment with FOLFOX chemotherapy in locally advanced rectal cancer |
| Abstract: | Strategies to enhance tumor immunogenicity may expand the role of immunotherapy beyond the mismatch repair-deficient subtype. In this pilot study, biopsies were performed at baseline and after four cycles of FOLFOX in eight patients receiving neoadjuvant chemotherapy for stage II/III locally advanced rectal cancer. Immunostaining was performed for T cell subsets (CD3+, CD8+, CD45RO+); macrophages (CD163+); T regulatory cells (FOXP3+); and expression of MHC class I, PD-1 and PD-L1. Changes in cell number or intensity were quantified and correlated with treatment response. Pretreatment patterns of immune infiltrates were mixed and did not correlate with treatment response. Posttreatment increases in T cell infiltrates (CD3+, CD8+ and CD45RO+) and MHC-I expression were observed in five patients. CD163+ cell numbers increased in four patients. FOXP3+ cell numbers increased in two patients, decreased in two other patients and remained unchanged in three patients. PD-1 scores increased in seven patients, and PD-L1 scores increased in four patients. Changes in tumor T cell responses did not correlate with treatment response. Changes in FOXP3+ cells were associated with treatment response in some patients: two patients with increases in FOXP3+ cells had poor responses, whereas the patient with the greatest reduction in FOXP3+ cells had a complete response. The patient with a complete clinical response had a much higher increase in MHC-I expression than other patients. These results suggest that chemotherapy can increase immune activity in the tumor microenvironment and could potentially be utilized to prime immune responses prior to immunomodulatory treatments. © 2018 Taylor & Francis Group, LLC. |
| Keywords: | neoadjuvant therapy; chemotherapy; t cells; immunotherapy; locally advanced rectal cancer; immune priming |
| Journal Title: | OncoImmunology |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 2162-4011 |
| Publisher: | Landes Bioscience |
| Date Published: | 2018-01-01 |
| Start Page: | e1435227 |
| Language: | English |
| DOI: | 10.1080/2162402x.2018.1435227 |
| PROVIDER: | scopus |
| PMCID: | PMC5980419 |
| PUBMED: | 29872576 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2018 -- Source: Scopus |
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