结直肠癌微环境中CD8肿瘤浸润淋巴细胞的增加促进了PD-L1表达的适应性免疫抵抗机制
2023-05-08 10:18阅读：
Increased CD8 Tumor Infiltrating Lymphocytes in
Colorectal Cancer Microenvironment Supports an
Adaptive Immune Resistance Mechanism of PD-L1
Ex*
Abstract
Background: Tumor cells express programmed death ligand-1 (PD-L1)
through several biological processes, thereby having
different clinical significance depending on the underlying
mechanism of ex*. Currently, mechanisms leading
to PDL1 gene ex* in colorectal cancer (CRC) are not fully
understood. Methods: We investigated 98
Indonesia CRC patients to determine PD-L1
protein ex*s and their correlations with PD-L1 gene copy number
status, tumor infiltrating lymphocytes (TILs),
tumor mutational profile, as well as clinicopathologic features.
Results: Our investigation demonstrated
that 18% of patients positively expressed P
D-L1. Further analysis on PD-L1 copy number revealed
that all PD-L1+ tumors had normal copy number, indicating that the
ex* of PD-L1 was not a consequence of genetic
amplification of PD-L1. From TILs analysis, there was a significant
increase of CD8 in all tumor cells ex* PD-L1
(P=0.0051), indicating that the inducible PD-L1 ex* was the
prominent mechanism occurred in CRC.
Furthermore, the ex* of PD-L1 in this CRC population was
significantly associated with high frequency of
MSI compared to the remainder PD-L1- tumors (P=0.0001), suggesting
the natural immunogenicity of tumors via MSI
status plays role in attracting immune response. On the other hand,
p53 mutations which were frequently observed
within Indonesian CRCs (76.5%), they were not associated with PD-L1
ex* (p=0.1108), as well as KRAS gene (29.6%;
p=0.5772) and BRAF gene mutations (5%; p=0.2171).
Conclusion: Our study demonstrated that
PD-L1 ex*s in CRC were predominantly found as a
consequence of infiltrating CD8 T lymphocytes that in
part arise in the setting of microsatellite
instability. Taken together, our findings further support the role
of adaptive immune resistance to drive PD-L1
induction in tumor microenvironment and may provide important
rationale for strategy implementation of
immunotherapy for CRC cases.
PD-L1的两种表达机制之前已经被证明。首先，肿瘤细胞上的PD-L1表达是由癌症驱动基因的改变决定的。第二，PD-L1的表达作为对宿主适应性免疫抵抗的反应是可诱导的。
该篇文章研究表明，CRC中PD-L1的表达主要是CD8
T淋巴细胞浸润的结果，这部分出现在微卫星不稳定的情况下。综上所述，我们的研究结果进一步支持了适应性免疫抵抗在肿瘤微环境中驱动PD-L1诱导的作用，并可能为CRC病例的免疫治疗策略实施提供重要的理论依据。
参考文献：
[1] Sudoyo, Aru W., et al. 'Increased CD8 tumor
infiltrating lymphocytes in colorectal cancer microenvironment
supports an adaptive immune resistance mechanism of PD-L1 ex*.'
Asian Pacific journal of cancer prevention: APJCP 20.11 (2019):
3421.
