The Potential Value of Immunotherapy in Colorectal Cancers: Review of the Evidence for Programmed Death-1 Inhibitor Therapy

Toh, James Wei Tatt; Souza, Paul de; Lim, Stephanie; Singh, Puneet; Chua, Wei; Ng, Wan; Spring, Kevin

doi:10.1016/j.clcc.2016.07.007

Cited by 73 publications

(45 citation statements)

References 52 publications

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“…Although the immunotherapy approaches still suffer from drawbacks including induced therapeutic resistance and immune‐related unfavorable outcomes, it is considered as one of the most successful strategies against CRC. Immunotherapy with anti‐PD‐1 agents has a possible advantage for immunogenic MSI‐H CRCs without any robust evidence to suggest the effectiveness of immunotherapy in MSS CRCs (Toh et al, 2016; C. M. Zhang et al, 2016). Different genetic alterations provide the opportunity for tumor cells to escape immune surveillance.…”

Section: Immune Responses and Immune Resistance In Crcmentioning

confidence: 99%

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PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Payandeh

Khalili

Somi

et al. 2020

Journal Cellular Physiology

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Colorectal cancer (CRC) is still considered as the third most frequent cancer in the world. Microsatellite instability (MSI), inflammation, and microRNAs have been demonstrated as the main contributing factors in CRC. Subtype 1 CRC is defined by NK cells infiltration, induction of Th1 lymphocyte and cytotoxic T cell responses as well as upregulation of immune checkpoint proteins including programmed cell death‐1 (PD‐1). Based on the diverse features of CRC, such as the stage and localization of the tumor, several treatment approaches are available. However, the efficiency of these treatments may be decreased due to the development of diverse resistance mechanisms. It has been proven that monoclonal antibodies (mAbs) can increase the effectiveness of CRC treatments. Nowadays, several mAbs including nivolumab and pembrolizumab have been approved for the treatment of CRC. Immune checkpoint receptors including PD‐1 can be inhibited by these antibodies. Combination therapy gives an opportunity for advanced treatment for CRC patients. In this review, an update has been provided on the molecular mechanisms involved in MSI colorectal cancer immune microenvironment by focusing on PD‐ligand 1 (PD‐L1) and treatment of patients with advanced immunotherapy, which were examined in the different clinical trial phases. Considering induced expression of PD‐L1 by conventional chemotherapeutics, we have summarized the role of PD‐L1 in CRC, the chemotherapy effects on the PD‐1/PD‐L1 axis and novel combined approaches to enhance immunotherapy of CRC by focusing on PD‐L1.

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Section: Immune Responses and Immune Resistance In Crcmentioning

confidence: 99%

“…Immunotherapy with anti-PD-1 agents has a possible advantage for immunogenic MSI-H CRCs without any robust evidence to suggest the effectiveness of immunotherapy in MSS CRCs (Toh et al, 2016; C. M. Zhang et al, 2016). Different genetic alterations provide the opportunity for tumor cells to escape immune surveillance.…”

Section: Features Of Cms1mentioning

confidence: 99%

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Payandeh

Khalili

Somi

et al. 2020

Journal Cellular Physiology

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“…In any case, it is clear that, even for patients with few gene mutations, immune reactions are difficult to trigger even by blocking natural immunosuppressive functions. Thus, it may not be possible to induce cancer regression in such cases, unless shared antigens like GPC3 are targeted in addition to neoantigens.…”

Section: Introductionmentioning

confidence: 99%

“…functions. Thus, it may not be possible to induce cancer regression in such cases, 6 unless shared antigens like GPC3 are targeted in addition to neoantigens.…”

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confidence: 99%

Cancer immunotherapy‐targeted glypican‐3 or neoantigens

et al. 2018

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Immune checkpoint inhibitors have ushered in a new era in cancer therapy, although other therapies or combinations thereof are still needed for many patients for whom these drugs are ineffective. In this light, we have identified glypican‐3 an HLA‐24, HLA‐A2 restriction peptide with extreme cancer specificity. In this paper, we summarize results from a number of related clinical trials showing that glypican‐3 peptide vaccines induce specific CTLs in most patients (UMIN Clinical Trials Registry: UMIN000001395, UMIN000005093, UMIN000002614, UMN000003696, and UMIN000006357). We also describe the current state of personalized cancer immunotherapy based on neoantigens, and assess, based on our own research and experience, the potential of such therapy to elicit cancer regression. Finally, we discuss the future direction of cancer immunotherapy.

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“…Antibody-mediated blockade of PDCD1 (PD-1) or CD274 (PD-L1) has recently emerged as a promising novel method of cancer immunotherapy, particularly in MSI cancer patients. [24][25][26][27][28] Although a substantial proportion of approximately half of advanced MSI cancer patients showed objective responses to anti-PDCD1 (PD-1) antibody therapy, even including radiographic complete responses in almost 20%, about one fourth of patients had progressive disease under therapy. 27 So far, markers predicting the success of anti-PDCD1 (PD-1)/CD274 (PD-L1) therapy among MSI cancer patients are not yet established.…”

Section: Introductionmentioning

confidence: 99%

High numbers of PDCD1 (PD-1)-positive T cells and B2M mutations in microsatellite-unstable colorectal cancer

et al. 2017

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2018) High numbers of PDCD1 (PD-1)-positive T cells and B2M mutations in microsatellite-unstable colorectal cancer, OncoImmunology, 7:2, e1390640, ABSTRACT DNA mismatch repair (MMR)-deficient cancers accumulate high numbers of coding microsatellite mutations, which lead to the generation of highly immunogenic frameshift peptide (FSP) neoantigens. MMR-deficient cells can grow out to clinically manifest cancers either if they evade immune cell attack or if local T-cells get exhausted. Therefore, a subset of MSI cancer patients responds particularly well to treatment with immune checkpoint inhibitors. We analyzed whether immune evasion in MMR-deficient cancer mediated by loss of HLA class I or II antigens is related to local immune cell activation status. Microsatellites located in Beta2-microglobulin (B2M) and the HLA class II-regulatory genes RFX5 and CIITA were analyzed for mutations in MMR-deficient colorectal cancers (n D 53). The results were related to CD3positive and PDCD1 (PD-1)-positive T-cell infiltration. PDCD1 (PD-1)-positive T-cell counts were significantly higher in B2M-mutant compared to B2M-wild type tumors (median: 22.2 cells per 0.25 mm 2 vs. 2.0 cells per 0.25 mm 2 , Wilcoxon test p D 0.002). Increasing PDCD1 (PD-1)-positive T-cell infiltration was significantly related to an increased likelihood of B2M mutations (OR D 1.81). HLA class II antigen expression status was significantly associated with enhanced overall T-cell infiltration, but not related to PDCD1 (PD-1)-positive Tcells. These results suggest that immune evasion mediated by B2M mutation-induced loss of HLA class I antigen expression predominantly occurs in an environment of activated PDCD1 (PD-1)-positive T cell infiltration. If B2M mutations interfere with anti-PDCD1 (PD-1)/CD274 (PD-L1) therapy success, we predict that resistance towards anti-PDCD1 (PD-1) therapy maycounterintuitivelybe particularly common in patients with MMR-deficient cancers that show high PDCD1 (PD-1)-positive T cell infiltration.

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The Potential Value of Immunotherapy in Colorectal Cancers: Review of the Evidence for Programmed Death-1 Inhibitor Therapy

Cited by 73 publications

References 52 publications

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

PD‐1/PD‐L1‐dependent immune response in colorectal cancer

Cancer immunotherapy‐targeted glypican‐3 or neoantigens

High numbers of PDCD1 (PD-1)-positive T cells and B2M mutations in microsatellite-unstable colorectal cancer

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