Beta-2-microglobulin positive tumor cells and CD8 positive lymphocytes are associated with outcome in post-neoadjuvant colorectal cancer resections

Abstract

Locally advanced colorectal cancers are treated with neoadjuvant therapy (NAT), which has been shown to alter the characteristics of the tumor including size, lymph node yield, and histologic grade. We seek to interrogate the effect of NAT on the immune microenvironment. We compared 190 patients with colorectal adenocarcinoma treated with NAT with those without NAT (n = 926). We evaluated clinicopathologic and molecular factors and performed immunohistochemistry and quantification on tissue microarrays for HLA class I/II proteins, beta-2-microglobulin (B2M), CD8, CD163, LAG3, PD-L1, and FoxP3. Patients in the NAT group were younger (60.9 vs 67.9, p < 0.001) and more often male (59.5 vs. 47.9, p = 0.004) than those in the non-NAT group. Tumors in the NAT group were smaller (3.5 vs 4.7 cm, p < 0.001), less often high grade (6.5% vs. 16.2%, p = 0.001), more frequently in the rectum (68.9% vs. 6.6%, p < 0.001) and associated with lower lymph node yields (p = 0.002); however, the incidence of extramural venous invasion, perineural invasion, and AJCC stage 3–4 disease were not different. Immune cells positive for CD8 (p = 0.011) were significantly lower in the NAT group. A high number of CD8⁺ cells and higher expression of B2M in tumor cells showed a significant survival benefit in both NAT and non-NAT group. NAT is associated with an immune-low tumor environment. CD8⁺ cells and tumor B2M expression may help identify a subset of immune high-tumors following NAT. This identification could aid in determining patients who may benefit from conservative management of colorectal carcinomas.