Patients with colorectal liver metastases (CLM) commonly receive neoadjuvant chemotherapy (NACT) prior to surgical resection. NACT may induce immunogenic cell death with subsequent recruitment of T-cells to the tumor microenvironment, which could be exploited by immune checkpoint inhibition (ICI). In theory, this could expand the use of ICI to obtain responses also in microsatellite stable colorectal cancer, but evidence to suggest optimal treatment schedules are lacking. In this study, densities of total-, cytotoxic-, helper- and regulatory T-cells were quantified by immunohistochemistry in resected CLM from 92 patients included in the OSLO-COMET trial (NCT01516710). All but one patient had microsatellite stable tumors (91/92). Associations between T-cell densities and clinicopathological parameters were analyzed. Fluoropyrimidine-based NACT (in most cases with addition of oxaliplatin or irinotecan) was administered to 45 patients completed median 8 weeks prior to surgical resection. No overall association was found between NACT administration and intratumoral T-cell densities. However, within the NACT group, a short time interval (<9.5 weeks) between NACT completion and CLM resection was strongly associated with high intratumoral T-cell densities compared to the long-interval and no NACT groups (medians 491, 236, and 292 cells/mm2, respectively; P < .0001). The results from this study suggest that the observed increase in intratumoral T-cells after NACT administration may be transient. The significance of this finding should be further explored to ensure that optimal treatment schedules are chosen for studies combining cytotoxic chemotherapy and ICI.

中文翻译：

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新辅助化疗与微卫星稳定结直肠肝转移瘤内T细胞密度的短暂增加有关。

大肠肝转移（CLM）患者通常在手术切除之前接受新辅助化疗（NACT）。NACT可能诱导免疫原性细胞死亡，随后将T细胞募集到肿瘤微环境中，可以通过免疫检查点抑制（ICI）加以利用。从理论上讲，这可能会扩展ICI在微卫星稳定结直肠癌中获得应答的作用，但缺乏表明最佳治疗方案的证据。在这项研究中，通过免疫组织化学在OSLO-COMET试验（NCT01516710）中对92例切除的CLM中的免疫组织化学方法定量了总T细胞，细胞毒性T细胞，辅助细胞和调节性T细胞的密度。除一名患者外，所有患者均患有微卫星稳定肿瘤（91/92）。分析了T细胞密度与临床病理参数之间的关联。在手术切除前8周中位完成治疗的45例患者中，使用基于氟嘧啶的NACT（在大多数情况下添加奥沙利铂或伊立替康）。在NACT给药和肿瘤内T细胞密度之间未发现总体关联。然而，在NACT组中，与长间隔和无NACT组相比，NACT完成和CLM切除之间的短时间间隔（<9.5周）与高瘤内T细胞密度密切相关（中位数491、236和292）单元格/ mm2; P <.0001）。这项研究的结果表明，观察到的NACT给药后肿瘤内T细胞的增加可能是短暂的。应该进一步探索这一发现的意义，以确保为结合细胞毒性化学疗法和ICI的研究选择最佳治疗方案。