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.

Keywords

• chemotherapy
• immunotherapy
• immune priming
• locally advanced rectal cancer
• neoadjuvant therapy
• t cells