Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)

Choucair, Khalil; Radford, Maluki; Bansal, Ajay; Park, Robin; Saeed, Anwaar

doi:10.3892/ijo.2021.5254

Cited by 9 publications

(5 citation statements)

References 127 publications

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“…Lynch syndrome-related CRC almost always exhibits MSI-H/dMMR, characterized by microsatellite sequence frameshift mutations that lead to a series of downstream codon changes and subsequent production of FSP. 26 Since FSPs are neoantigens, tumor cells acquire high immunogenicity and can be recognized by CD8 + T cells, making this type of cancer potentially more sensitive to ICIs. 27 In fact, many ICIs have been clinically proven to be highly effective in MSI-H/dMMR CRC.…”

Section: Discussionmentioning

confidence: 99%

Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer

Wang,

Zhong,

Huang

et al. 2024

ACS Biomater. Sci. Eng.

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Treatment with immune checkpoint inhibitors (ICIs) has shown efficacy in some patients with Lynch syndrome-associated colon cancer, but some patients still do not benefit from it. In this study, we adopted a combination strategy of tumor vaccines and ICIs to maximize the benefits of immunotherapy. Here, we obtained tumor-antigencontaining cell lysate (TCL) by lysing MC38 Mlh1 KD cells and prepared liposome nanoparticles (Lipo-PEG) with a typical spherical morphology by thin-film hydration. Anti-PD-L1 was coupled to the liposome surface by the amidation reaction. As observed, anti-PD-L1/TCL@Lipo-PEG was not significantly toxic to mouse intestinal epithelial cells (MODE-K) in the safe concentration range and did not cause hemolysis of mouse red blood cells. In addition, anti-PD-L1/TCL@Lipo-PEG reduced immune escape from colon cancer cells (MC38 Mlh1 KD ) by the anti-PD-L1 antibody, restored the killing function of CD8 + T cells, and targeted more tumor antigens to bone marrow-derived dendritic cells (BMDCs), which also expressed PD-L1, to stimulate BMDC antigen presentation. In syngeneic transplanted Lynch syndrome-associated colon cancer mice, the combination of anti-PD-L1 and TCL provided better cancer suppression than monoimmunotherapy, and the cancer suppression effect of anti-PD-L1/TCL@Lipo-PEG treatment was even better than that of the free drug. Meanwhile anti-PD-L1/TCL@Lipo-PEG enhanced the immunosuppressive tumor microenvironment. In vivo fluorescence imaging and H&E staining showed that the nanomedicine was mainly retained in the tumor site and had no significant toxic side effects on other major organs. The anti-PD-L1/TCL@Lipo-PEG prepared in this study has high efficacy and good biosafety in alleviating the progression of Lynch syndrome-associated colon cancer, and it is expected to be a therapeutic candidate for Lynch syndrome-associated colon cancer.

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Section: Discussionmentioning

confidence: 99%

Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer

Wang,

Zhong,

Huang

et al. 2024

ACS Biomater. Sci. Eng.

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“…SNVS, single-nucleotide variants; indels, insertions/deletions. cancer and paving the way for immunotherapy targeting neoantigens 21,22 (Figure 2). Particularly, TMB has become an emerging clinical biomarker.…”

Section: Small Insertion/deletion Contributes To the Emergence Of Neo...mentioning

confidence: 99%

“…FSP uses major histocompatibility complex (MHC) class I and class II molecules as substrates for antigen presentation. When presented on the cell surface, the neoantigens can serve as the target of CD4 + helper T lymphocytes and CD8 + cytotoxic T lymphocytes (CTL) for tumour infiltration, thus enhancing the immunity to cancer and paving the way for immunotherapy targeting neoantigens 21,22 (Figure 2). Particularly, TMB has become an emerging clinical biomarker.…”

Section: Colorectal Cancer and Neoantigensmentioning

confidence: 99%

Personalised neoantigen‐based therapy in colorectal cancer

Zhu,

Li,

Chen

et al. 2023

Clinical & Translational Med

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Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer‐specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti‐tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen‐based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen‐based therapy holds great promise as an effective treatment approach for patients with CRC.

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“…In the last decade, numerous monoclonal antibodies targeting the PD-1 and its ligand PD-L1 have been approved for the treatment of all types of human cancer. In colorectal cancer, such antibodies have been approved for the treatment of cases with MMR deficiency and microsatellite instability [54]. The striking clinical evidence of dostarlimab anti-PD1 monotherapy eliminating 100% of locally advanced rectal cancer in a small cohort of patients with MMR-deficient rectal tumors may revolutionize our therapeutic policies against rectal cancer [6].…”

Section: Pd-1/pd-l1 Pathwaymentioning

confidence: 99%

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

Koukourakis

Platoni

Tiniakos

et al. 2023

CIMB

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It is well-established that tumor antigens and molecules expressed and secreted by cancer cells trigger innate and adaptive immune responses. These two types of anti-tumor immunity lead to the infiltration of the tumor’s microenvironment by immune cells with either regulatory or cytotoxic properties. Whether this response is associated with tumor eradication after radiotherapy and chemotherapy or regrowth has been a matter of extensive research through the years, mainly focusing on tumor-infiltrating lymphocytes and monocytes and their subtypes, and the expression of immune checkpoint and other immune-related molecules by both immune and cancer cells in the tumor microenvironment. A literature search has been conducted on studies dealing with the immune response in patients with rectal cancer treated with neoadjuvant radiotherapy or chemoradiotherapy, assessing its impact on locoregional control and survival and underlying the potential role of immunotherapy in the treatment of this cancer subtype. Here, we provide an overview of the interactions between local/systemic anti-tumor immunity, cancer-related immune checkpoint, and other immunological pathways and radiotherapy, and how these affect the prognosis of rectal cancer patients. Chemoradiotherapy induces critical immunological changes in the tumor microenvironment and cancer cells that can be exploited for therapeutic interventions in rectal cancer.

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Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)

Cited by 9 publications

References 127 publications

Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer

Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer

Personalised neoantigen‐based therapy in colorectal cancer

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

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