Heterogeneity of PD-L1 expression and CD8 lymphocyte infiltration in metastatic colorectal cancer and their prognostic significance

Xin, Haisong; Zhou, Chenguang; Wang, Guanglin; Zhang, Juan; Liu, Youqiang; Li, Baokun; Zhang, Jianfeng; Su, Mingming; Wang, Guiying

doi:10.1016/j.heliyon.2023.e13048

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…Based on the results of this study, TILs CD8+ expression and clinicopathological factors in CRC patients did not show an interrelated relationship. However, based on other studies linking TILs CD8+ expression with survival in CRC patients, it showed a positive relationship between TILs CD8+ expression and increased survival in 85 patients [38] . Chemotherapeutic agents are intended to trigger particular immune responses that lead to the immunogenic death of cancer cells.…”

Section: Expression Of Tumor Infiltrating Lymphocytes Cd8+ In Colorec...mentioning

confidence: 94%

Intra‐tumoral tumor infiltrating Lymphocyte‐T CD8+ and chemotherapy response in colorectal cancer: A prospective observational study

Budiman,

Lukman,

Rudiman

et al. 2024

Trends Immunother.

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Background: The immunotherapy approach to colorectal cancer is becoming one of the key approaches to colorectal cancer treatment. One of the components of immune responses is tumor‐infiltrating lymphocyte CD8+ cells (TILs CD8+). While chemotherapy is one of the main treatments for colorectal cancer, we need to consider immunotherapy for advanced colorectal cancer. Thus, this study is aimed at finding the association between TIL CD8+ expression and chemotherapy response. Methods: This is a prospective cohort study with colorectal cancer patients in the Digestive Surgery division of a tertiary general hospital in West Java, Indonesia. An immunohistochemistry examination was used to evaluate the expression of TIL CD8+. The response evaluation criteria in solid tumors (RECIST) were used for the evaluation of chemotherapy response. Results: There were 53 research subjects included. There were 20 (37.7%) subjects with high expression of TILs CD8+; there were 30 (56.6%) subjects in stage III, followed by stage IV (17.32%) and stage II (6.11%). There were 18 subjects (34%) who showed progressive disease, 17 subjects (32.1%) showed partial response, and 16 subjects (30.2%) with high expression of TILs CD8+ showed partial chemotherapy response. The TILs CD8+ expression showed no significant relationship with age, sex, subtype, grade, or tumor location, but showed a significant relationship with stage and chemotherapy response (P < 0.05). Conclusion: High TILs CD8+ expression show a relationship with better chemotherapy response and a better prognosis based on disease stage in colorectal cancer patients.

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Section: Expression Of Tumor Infiltrating Lymphocytes Cd8+ In Colorec...mentioning

confidence: 94%

Intra‐tumoral tumor infiltrating Lymphocyte‐T CD8+ and chemotherapy response in colorectal cancer: A prospective observational study

Budiman,

Lukman,

Rudiman

et al. 2024

Trends Immunother.

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“…This finding has since been corroborated by subsequent research and underscores the importance of TILs in progressing and managing CRC (153)(154)(155). In a recent study, Xin et al (106) determined that more CD8 + lymphocyte infiltration in either primary tumors or paired distant metastases predicted an excellent prognosis (P-value =0.036 and 0.031, respectively). In multivariate analysis, CD8 + TIL density in primary tumors was an independent predictive factor for OS (HR= 0.28, 95% CI= 0.09-0.93, P-value =0.038) (106).…”

Section: Colorectal Cancermentioning

confidence: 99%

The molecular mechanism of actions and clinical utilities of tumor infiltrating lymphocytes in gastrointestinal cancers: a comprehensive review and future prospects toward personalized medicine

Piroozkhah,

Gholinezhad,

Piroozkhah

et al. 2023

Front. Immunol.

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Gastrointestinal (GI) cancers remain a significant global health burden, accounting for a substantial number of cases and deaths. Regrettably, the inadequacy of dependable biomarkers hinders the precise forecasting of patient prognosis and the selection of appropriate therapeutic sequencing for individuals with GI cancers, leading to suboptimal outcomes for numerous patients. The intricate interplay between tumor-infiltrating lymphocytes (TILs) and the tumor immune microenvironment (TIME) has been shown to be a pivotal determinant of response to anti-cancer therapy and consequential clinical outcomes across a multitude of cancer types. Therefore, the assessment of TILs has garnered global interest as a promising prognostic biomarker in oncology, with the potential to improve clinical decision-making substantially. Moreover, recent discoveries in immunotherapy have progressively changed the landscape of cancer treatment and significantly prolonged the survival of patients with advanced cancers. Nonetheless, the response rate remains constrained within solid tumor sufferers, even when TIL landscapes appear comparable, which calls for the development of our understanding of cellular and molecular cross-talk between TIME and tumor. Hence, this comprehensive review encapsulates the extant literature elucidating the TILs’ underlying molecular pathogenesis, prognostic significance, and their relevance in the realm of immunotherapy for patients afflicted by GI tract cancers. Within this review, we demonstrate that the type, density, and spatial distribution of distinct TIL subpopulations carries pivotal implications for the prediction of anti-cancer treatment responses and patient survival. Furthermore, this review underscores the indispensable role of TILs in modulating therapeutic responses within distinct molecular subtypes, such as those characterized by microsatellite stability or programmed cell death ligand-1 expression in GI tract cancers. The review concludes by outlining future directions in TIL-based personalized medicine, including integrating TIL-based approaches into existing treatment regimens and developing novel therapeutic strategies that exploit the unique properties of TILs and their potential as a promising avenue for personalized cancer treatment.

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“…The OAK study investigating the efficacy of atezolizumab (an anti-PD-L1 antibody) showed that the treatment of PD-L1-negative NSCLC with atezolizumab led to improved survival rates compared to docetaxel treatment [10]. This underscores the suboptimal predictive value of PD-L1 expression, which, among other things, can be explained by a high degree of tissue heterogeneity [11][12][13]. In light of these findings, it becomes evident that additional biomarkers are needed.…”

Section: Introductionmentioning

confidence: 99%

Plasma Immune Proteins and Circulating Tumor DNA Predict the Clinical Outcome for Non-Small-Cell Lung Cancer Treated with an Immune Checkpoint Inhibitor

Stensgaard,

Thomsen,

Helstrup

et al. 2023

Cancers

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Immunotherapy has altered the therapeutic landscape for patients with non-small-cell lung cancer (NSCLC). The immune checkpoint inhibitor pembrolizumab targets the PD-1/PD-L1 signaling axis and produces durable clinical responses, but reliable biomarkers are lacking. Using 115 plasma samples from 42 pembrolizumab-treated patients with NSCLC, we were able to identify predictive biomarkers. In the plasma samples, we quantified the level of 92 proteins using the Olink proximity extension assay and circulating tumor DNA (ctDNA) using targeted next-generation sequencing. Patients with an above-median progression-free survival (PFS) had significantly higher expressions of Fas ligand (FASLG) and inducible T-cell co-stimulator ligand (ICOSLG) at baseline than patients with a PFS below the median. A Kaplan–Meier analysis demonstrated that high levels of FASLG and ICOSLG were predictive of longer PFS and overall survival (OS) (PFS: 10.83 vs. 4.49 months, OS: 27.13 vs. 18.0 months). Furthermore, we identified a subgroup with high expressions of FASLG and ICOSLG who also had no detectable ctDNA mutations after treatment initiation. This subgroup had significantly longer PFS and OS rates compared to the rest of the patients (PFS: 25.71 vs. 4.52 months, OS: 34.62 vs. 18.0 months). These findings suggest that the expressions of FASLG and ICOSLG at baseline and the absence of ctDNA mutations after the start of treatment have the potential to predict clinical outcomes.

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Heterogeneity of PD-L1 expression and CD8 lymphocyte infiltration in metastatic colorectal cancer and their prognostic significance

Cited by 6 publications

References 40 publications

Intra‐tumoral tumor infiltrating Lymphocyte‐T CD8+ and chemotherapy response in colorectal cancer: A prospective observational study

Intra‐tumoral tumor infiltrating Lymphocyte‐T CD8+ and chemotherapy response in colorectal cancer: A prospective observational study

The molecular mechanism of actions and clinical utilities of tumor infiltrating lymphocytes in gastrointestinal cancers: a comprehensive review and future prospects toward personalized medicine

Plasma Immune Proteins and Circulating Tumor DNA Predict the Clinical Outcome for Non-Small-Cell Lung Cancer Treated with an Immune Checkpoint Inhibitor

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