Abstract A102: The prognostic impact of different immune landscapes in patients with stage I-III colorectal cancer
Authors: Inthagard Jitwadee , McMillan Donald , Edwards Joanne , Roseweir Antonia 
Published: March 2020

Background: Colorectal cancer (CRC), is an inflammatory disease, with a mix of lymphoid and myeloid cells found within the tumor microenvironment. These immune cells can function as antitumorigenic or protumorigenic; therefore, it is important to evaluate all immune cell types within a patient’s tumor to understand the effects of each immune landscape on patient survival. Therefore, this study investigated the immune landscape of patients with stage I-III CRC to assess the effect of individual immune cell types and different immune landscapes on prognosis.

Method: Immunohistochemistry for lymphoid and myeloid immune cells (CD3, CD8, FoxP3, CD45RO, CD68, CD80, CD163, and CD66b) was performed in 930 patients with stage I-III CRC on tissue microarrays. Cell counts were performed at three hotspots within the tumor nests and stroma separately and an average count was taken. Receiver operated curve (ROC) analysis was utilized to define cut-offs for weak and strong expression. Immune cells and immune landscapes were analyzed for associations with cancer-specific survival (CSS).

Results: For tumor-infiltrating and stromal lymphoid cells, high CD3+ (both p&lt;0.001), high CD8+ (both p&lt;0.001), and high FoxP3+ (both p&lt;0.001) T lymphocytes were significantly associated with improved CSS. Furthermore, tumor-infiltrating CD3+ T lymphocytes (HR 0.29, 95% CI 0.13-0.66, p=0.003) were independently associated with CSS. For tumor-infiltrating myeloid cells, high CD68+ (p=0.018), high CD80+ (p=0.017), and low CD66b+ (p=0.035) cells were significantly associated with improved CSS. For stromal myeloid cells, low CD68+ (p=0.044), high CD80+ (p=0.015), low CD163+ (p=0.031), and high CD66b+ (p=0.021) cells were significantly associated with improved CSS. Furthermore, stromal CD68+ (HR 8.78, 95% CI 3.53-21.82, p&lt;0.001), and CD80+ (HR 0.28, 95% CI 0.11-0.68, p=0.005) cells independently associated with CSS. To assess different immune landscapes, CD3+/CD68+/CD66b+ were combined and divided into four landscapes; 1) all low, 2) only myeloid cells high, 3) only T cells high, and 4) both T cells + myeloid cells high. When assessed for effects on prognosis in tumor cells, patients with both high T cells + myeloid cells had significantly better CSS, whereas patients with only high myeloid cells had significantly poorer CSS (p&lt;0.001). No significant effects were seen in the stroma; however, a similar trend was noted (p=0.052).

Conclusion: The results of this study confirm that different immune cell subtypes associate with different prognosis in patients with stage I-III CRC. Elevated lymphoid cells always associate with improved prognosis independent of the presence of myeloid cells, whereas patients with only elevated myeloid cells have a poorer prognosis. Overall, the results suggest that assessing different immune landscapes utilizing broad markers for T lymphocytes, macrophages, and granulocytes could aid clinicians with patient prognosis and help target appropriate patients for immunotherapy.

Citation Format: Jitwadee Inthagard, Donald McMillan, Joanne Edwards, Antonia Roseweir. The prognostic impact of different immune landscapes in patients with stage I-III colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A102.