Advances in adoptive cellular therapy for colorectal cancer: a narrative review

Yi, Xing; Hu, Wenwei

doi:10.21037/atm-22-6196

Cited by 6 publications

(4 citation statements)

References 151 publications

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“…While survival rates in CMS1 patients have improved upon combination with immune checkpoint inhibitors, only a fraction of these patients responds to the treatment [ 4 ]. Besides ICI, chimeric antigen receptor-T (CAR-T) cell safety and efficacy are also being evaluated in CRC in phase I clinical trials [ 5 , 6 , 7 , 8 ]. One alternative to targeting tumor antigens in cell therapy relies on the detection of stress-induced ligands, such as ligands for the activating receptor NKG2D, known to be expressed in most cancer types [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

NKG2D Fine-Tunes the Local Inflammatory Response in Colorectal Cancer

Curio

Lin

Bromley

et al. 2023

Cancers

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Treating colorectal cancer (CRC) is a major challenge due to the heterogeneous immunological, clinical and pathological landscapes. Immunotherapy has so far only proven effective in a very limited subgroup of CRC patients. To better define the immune landscape, we examined the immune gene expression profile in various subsets of CRC patients and used a mouse model of intestinal tumors to dissect immune functions. We found that the NK cell receptor, natural-killer group 2 member D (NKG2D, encoded by KLRK1) and NKG2D ligand gene expression is elevated in the most immunogenic subset of CRC patients. High level of KLRK1 positively correlated with the mRNA expression of IFNG and associated with a poor survival of CRC patients. We further show that NKG2D deficiency in the Apcmin/+ mouse model of intestinal tumorigenesis led to reduced intratumoral IFNγ production, reduced tumorigenesis and enhanced survival, suggesting that the high levels of IFNγ observed in the tumors of CRC patients may be a consequence of NKG2D engagement. The mechanisms governing the contribution of NKG2D to CRC progression highlighted in this study will fuel discussions about (i) the benefit of targeting NKG2D in CRC patients and (ii) the need to define the predictive value of NKG2D and NKG2D ligand expression across tumor types.

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Section: Introductionmentioning

confidence: 99%

NKG2D Fine-Tunes the Local Inflammatory Response in Colorectal Cancer

Curio

Lin

Bromley

et al. 2023

Cancers

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“…TCR-T cell therapy showed promising results and even significantly higher benefits compared to TILs for cutaneous melanoma [ 110 ]. They had good potential for colorectal cancer and leukemia treatment [ 111 , 112 ]. However, TCR-cells therapy implies several challenges such as the importance of the target antigen selection, immune escape, safety and toxicity, cytokine storms, and T cell exhaustion.…”

Section: Strategies To Turn Non-inflamed Cold Tumors Into Inflamed Ho...mentioning

confidence: 99%

Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy

Benoit

Vogin

Duhem

et al. 2023

Cells

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Immunotherapy includes immune checkpoint inhibitors (ICI) such as antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death protein/programmed death ligand 1 (PD-1/PD-L1) axis. Experimental and clinical evidence show that immunotherapy based on immune checkpoint inhibitors (ICI) provides long-term survival benefits to cancer patients in whom other conventional therapies have failed. However, only a minority of patients show high clinical benefits via the use of ICI alone. One of the major factors limiting the clinical benefits to ICI can be attributed to the lack of immune cell infiltration within the tumor microenvironment. Such tumors are classified as “cold/warm” or an immune “desert”; those displaying significant infiltration are considered “hot” or inflamed. This review will provide a brief summary of different tumor properties contributing to the establishment of cold tumors and describe major strategies that could reprogram non-inflamed cold tumors into inflamed hot tumors. More particularly, we will describe how targeting hypoxia can induce metabolic reprogramming that results in improving and extending the benefit of ICI.

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“…T cells hardly exert several cell functions associated with hypofunction, cell exhaustion, and reduced efficacy, possibly resulting in treatment failure [132]. Procuring infusion of a higher T cell ratio can extend the effective cells; however, it may be inconvenient for advanced CRC as it may demand more time to manufacture [133].…”

Section: Limitations Of Cellular Therapy On Advanced Crc Treatmentmentioning

confidence: 99%

Cell Therapy as Target Therapy against Colon Cancer Stem Cells

Garza-Treviño

Quiroz-Reyes

Rojas-Murillo

et al. 2023

IJMS

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Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with properties, such as self-renewal, differentiation, and tumorigenicity. CSCs have been proposed as a plausible therapeutic target as they are responsible for tumor recurrence, metastasis, and conventional therapy resistance. Selectively targeting CSCs is a promising strategy to eliminate the propagation of tumor cells and impair overall tumor development. Recent research shows that several immune cells play a crucial role in regulating tumor cell proliferation by regulating different CSC maintenance or proliferation pathways. There have been great advances in cellular immunotherapy using T cells, natural killer (NK) cells, macrophages, or stem cells for the selective targeting of tumor cells or CSCs in colorectal cancer (CRC). This review summarizes the CRC molecular profiles that may benefit from said therapy and the main vehicles used in cell therapy against CSCs. We also discuss the challenges, limitations, and advantages of combining conventional and/or current targeted treatments in the late stages of CRC.

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Advances in adoptive cellular therapy for colorectal cancer: a narrative review

Cited by 6 publications

References 151 publications

NKG2D Fine-Tunes the Local Inflammatory Response in Colorectal Cancer

NKG2D Fine-Tunes the Local Inflammatory Response in Colorectal Cancer

Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy

Cell Therapy as Target Therapy against Colon Cancer Stem Cells

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