Latest evidence on immune checkpoint inhibitors in metastatic colorectal cancer: A 2022 update

Boukouris, Aristeidis E.; Theochari, Maria; Stefanou, Dimitra; Papalambros, Alexandros; Felekouras, Evangelos; Gogas, Helen; Ziogas, Dimitriοs

doi:10.1016/j.critrevonc.2022.103663

Cited by 51 publications

(27 citation statements)

References 122 publications

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“…The efficacy of anti-PD-1/PD-L1 antibodies has been well demonstrated in various types of cancer, including MSI-H CRC [ 64 , 65 ]. However, dMMR/MSI-H CRC comprises approximately 5% of metastatic CRC, and the efficacy of ICIs has been unsatisfactory in the majority of CRC which is mismatch repair proficient (pMMR) or microsatellite stable (MSS) [ 66 , 67 ]. Because MSS metastatic CRC is usually classified as a typical “cold” cancer that presents a lack of the activation of immune responses, the studies investigating how to generate a “hot” TME are critical to the treatment improvement of MSS CRC [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

Chung

Liao

Lin

et al. 2022

IJMS

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Programmed death-ligand 1 (PD-L1) is an immune checkpoint molecule that can regulate immune responses in the tumor microenvironment (TME); however, the clinical applications of PD-L1 in early-stage colorectal cancer (CRC) remain unclear. In this study, we aimed to investigate the relationship between PD-L1 expression and survival outcome and explore its relevant immune responses in CRC. PD-L1 expression was evaluated by immunohistochemical staining to determine the tumor proportion score and combined positive score (CPS) in a Taiwanese CRC cohort. The oncomine immune response research assay was conducted for immune gene expression analyses. CRC datasets from the TCGA database were reappraised for PD-L1-associated gene enrichment analyses using GSEA. The high expression of PD-L1 (CPS ≥ 5) was associated with longer recurrence-free survival (p = 0.031) and was an independent prognostic factor as revealed by multivariate analysis. High PD-L1 expression was related to six immune-related gene signatures, and CXCL9 is the most significant overexpressed gene in differential analyses. High CXCL9 expression correlated with increased infiltration levels of immune cells in the TME, including CD8+ T lymphocytes and M1 macrophages. These findings suggest that high PD-L1 expression is a prognostic factor of early-stage CRC, and CXCL9 may play a key role in regulating PD-L1 expression.

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Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

Chung

Liao

Lin

et al. 2022

IJMS

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“…These mechanisms ultimately help the tumor to escape anti-tumor immunity [ 3 , 4 , 5 , 28 , 29 , 30 , 31 ]. Therefore, monoclonal antibodies have been developed to antagonize this inhibitory signaling, and in the last decade, several randomized clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 drugs [ 29 , 30 , 31 , 32 , 33 , 34 ]. The most immunological response is expected in those (metastatic) CRC patients who have tumors with deficient mismatch-repair and/or high levels of microsatellite instability [ 29 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…The most immunological response is expected in those (metastatic) CRC patients who have tumors with deficient mismatch-repair and/or high levels of microsatellite instability [ 29 , 35 , 36 ]. Most studies have reported promising results: a significantly improved overall survival and PFS, better response to treatment, and a higher occurrence of partial and complete responses have been found in those patients for whom almost no responses were observed previously [ 30 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, recent research has also described a significant interaction between the PD-1/PD-L1 axis and the EGFR pathway [ 28 ]. These mechanisms ultimately help the tumor to escape anti-tumor immunity [ 3 , 4 , 5 , 28 , 29 , 30 , 31 ]. Therefore, monoclonal antibodies have been developed to antagonize this inhibitory signaling, and in the last decade, several randomized clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 drugs [ 29 , 30 , 31 , 32 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Does Elevated Pre-Treatment Plasma PD-L1 Level Indicate an Increased Tumor Burden and Worse Prognosis in Metastatic Colorectal Cancer?

Dank

Mühl

Herold

et al. 2022

JCM

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Background: Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) have been reported as possibly favorable prognostic factors in colorectal cancer (CRC). However, their longitudinal effect is unknown. Methods: A pilot study was performed to investigate whether baseline PD-1/PD-L1 levels are associated with further laboratory changes and/or shorter survival. Results: A total of 506 laboratory measurements from 37 metastatic CRC patients were analyzed. The baseline plasma PD-1 and PD-L1 levels were 27.73 ± 1.20 pg/mL and 16.01 ± 1.09 pg/mL, respectively. Disease progression (p = 0.0443) and baseline high-sensitivity C-reactive protein (p = 0.0011), aspartate transaminase (p = 0.0253), alanine transaminase (p = 0.0386), and gamma-glutamyl transferase (p = 0.0103) were associated with higher PD-L1 levels. Based on the baseline PD-1/PD-L1 levels, low and high PD-1/PD-L1 groups were created. Constant, pathological levels of complete blood count values, high-sensitivity C-reactive protein, serum albumin, high-density lipoprotein cholesterol, and lactate dehydrogenase were characteristic for patients with high baseline PD-L1. High PD-L1 levels were significantly associated with increased tumor burden. Disease-specific survival and progression-free survival were significantly shorter in patients with high PD-L1. Conclusions: Abnormal levels of laboratory parameters and intensified tumor burden can be expected if elevated baseline plasma PD-1/PD-L1 levels are found.

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“…1 Current FDAapproved ICIs include the anti-CTLA-4 monoclonal antibody, ipilimumab; the anti-PD-1 monoclonal antibodies cemiplimab, dostarlimab, nivolumab, and pembrolizumab; the anti-PD-L1 monoclonal antibodies, atezolizumab, avelumab, and durvalumab; and the LAG-3 inhibitor, relatlimab. 7,8 These agents are indicated, alone or in combination, in the treatment of many cancers, including breast, cervical, colorectal, esophageal, endometrial, gastric, head and neck, Hodgkin lymphoma, kidney, liver, lung, skin, and melanoma. Typically dosed every 3-4 weeks, ICIs have significant variation in their half-lives, lasting days to weeks.…”

Section: Ici Mechanisms Of Actionmentioning

confidence: 99%

Therapeutic plasma exchange in the management of immune checkpoint inhibitor‐associated immune‐related adverse effects: A review

et al. 2022

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Latest evidence on immune checkpoint inhibitors in metastatic colorectal cancer: A 2022 update

Cited by 51 publications

References 122 publications

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

Does Elevated Pre-Treatment Plasma PD-L1 Level Indicate an Increased Tumor Burden and Worse Prognosis in Metastatic Colorectal Cancer?

Therapeutic plasma exchange in the management of immune checkpoint inhibitor‐associated immune‐related adverse effects: A review

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