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 10:18:14
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 PD-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.
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
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 PD-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.