Immunotherapy of colorectal cancer: Challenges for therapeutic efficacy

Ciardiello, Davide; Vitiello, Pietro Paolo; Cardone, Claudia; Martini, Giulia; Troiani, Teresa; Martinelli, Erika; Ciardiello, Fortunato

doi:10.1016/j.ctrv.2019.04.003

Cited by 238 publications

(210 citation statements)

References 117 publications

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“…As Guinney et al have pointed out [42], oncogene amplifications associated with CMS2 and the prominent metabolic activation of CMS3 tumors may be valuable tools for developing new therapeutic interventions in CRC patients. Several treatment strategies based on the 4 molecular subtypes of CRC have been proposed during the last years that could eventually overcome the absence of T cell infiltration and turn immunologically 'cold' tumors into 'hot' ones [44][45][46]. Research findings show that these approaches based on comprehensive analysis of CRC tumors have the potential to lead to customized treatments for individual patients, with improved clinical responses and fewer side effects.…”

Section: Immune Checkpoint Inhibitors In Pmmr Mcrcmentioning

confidence: 99%

“…Research findings show that these approaches based on comprehensive analysis of CRC tumors have the potential to lead to customized treatments for individual patients, with improved clinical responses and fewer side effects. years that could eventually overcome the absence of T cell infiltration and turn immunologically 'cold' tumors into 'hot' ones [44][45][46]. Research findings show that these approaches based on comprehensive analysis of CRC tumors have the potential to lead to customized treatments for individual patients, with improved clinical responses and fewer side effects.…”

Section: Immune Checkpoint Inhibitors In Pmmr Mcrcmentioning

confidence: 99%

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Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Damilakis

Mavroudis

Sfakianaki

et al. 2020

Cancers

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Immunotherapy has considerably increased the number of anticancer agents in many tumor types including metastatic colorectal cancer (mCRC). Anti-PD-1 (programmed death 1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) immune checkpoint inhibitors (ICI) have been shown to benefit the mCRC patients with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). However, ICI is not effective in mismatch repair proficient (pMMR) colorectal tumors, which constitute a large population of patients. Several clinical trials evaluating the efficacy of immunotherapy combined with chemotherapy, radiation therapy, or other agents are currently ongoing to extend the benefit of immunotherapy to pMMR mCRC cases. In dMMR patients, MSI testing through immunohistochemistry and/or polymerase chain reaction can be used to identify patients that will benefit from immunotherapy. Next-generation sequencing has the ability to detect MSI-H using a low amount of nucleic acids and its application in clinical practice is currently being explored. Preliminary data suggest that radiomics is capable of discriminating MSI from microsatellite stable mCRC and may play a role as an imaging biomarker in the future. Tumor mutational burden, neoantigen burden, tumor-infiltrating lymphocytes, immunoscore, and gastrointestinal microbiome are promising biomarkers that require further investigation and validation.

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Section: Immune Checkpoint Inhibitors In Pmmr Mcrcmentioning

confidence: 99%

Section: Immune Checkpoint Inhibitors In Pmmr Mcrcmentioning

confidence: 99%

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Damilakis

Mavroudis

Sfakianaki

et al. 2020

Cancers

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“…In the recent years, based on a better knowledge of the complex interactions between the immune system and the tumor microenvironment, immunotherapy has become a novel effective and promising therapeutic strategy for cancer, and its efficacy was widely tested by CRC model. The vast majority of CRC patients with deficient mismatch repair (dMMR) or highly microsatellite instable (MSI-H) benefit from immune checkpoint inhibitors, which is not effective in other CRC patients with proficient MMR (pMMR) or microsatellite stable (MSS) [4]. Patients with CRC do not respond to autologous tumour lysate DC (ADC) and peptide vaccines [4].…”

Section: Introductionmentioning

confidence: 99%

“…The vast majority of CRC patients with deficient mismatch repair (dMMR) or highly microsatellite instable (MSI-H) benefit from immune checkpoint inhibitors, which is not effective in other CRC patients with proficient MMR (pMMR) or microsatellite stable (MSS) [4]. Patients with CRC do not respond to autologous tumour lysate DC (ADC) and peptide vaccines [4]. T cells, which are engineered to express an affinity-enhanced T-cell receptor (TCR) or an antibody-based chimeric antigen receptor (CAR) targeting tumor associated antigens (TAAs), such as carcinoembryonic antigen (CEA) [5, 6] and human epidermal growth factor receptor-2 (HER2) [7], regress metastatic CRC, but simultaneously mediate severe autoimmunity in patients.…”

Section: Introductionmentioning

confidence: 99%

“…It has been shown that some cancers with high tumor mutational burden (TMB) possess a set of common neoantigens owing to the microsatellites [11]. The presence of microsatellite instability has been found in approximately 15-20% CRC, and dMMR CRC has a high TMB, which is far higher than the standard value [4]. Furthermore, driver mutations possess only 8% CD8 T-cell neo-epitopes, while passenger mutations possess 92% CD8 T-cell neo-epitopes and 100% CD4 T-cell neo-epitopes [9].…”

Section: Introductionmentioning

confidence: 99%

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The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic

Liang

Qin

et al. 2019

Preprint

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23Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the 24 world, as the result of the traditional treatments. Immunotherapy targeting neoantigens 25 can induce durable tumor regression in cancer patients, but is almost limited to 26 individual treatment, resulting from the unique neoantigens. Many shared oncogenic 27 mutations are detected, but whether the common neoantigens can be identified in CRC 28 is unknown. Using the somatic mutations data from 321 CRC patients combined with 29 a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-30 A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and 31 presentation score (EPIC>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 32 25 common neoantigens were proved to be naturally processed and presented on 33 constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common 34 neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) 35 to secrete IFN-. However, only 2 out of 25 common neoantigens were simultaneously 36 presented and immunogenic. Moreover, using cell-sorting technology combined with 37 single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 38 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens 39 with presentation and immunogenicity could be found in CRC, which would be 40 developed as the universal targets for CRC immunotherapy. 41 42 43 44 45 46 Colorectal cancer (CRC) is the third commonest diagnosed malignant cancer and 47 the second leading cause of cancer death in the world [1]. In 2018, more than 1.8 48 million new cases of CRC and almost 881 thousand cases of CRC-interrelated death 49 occurred in the world [1], and the global burden of CRC is estimated to reach over 2.2 50 million new cases and 1.1 million cancer deaths by 2030 [2]. Traditionally surgical 51 resection can cure the early stage of CRC, but about 50% of patients ultimately die of 52 distant metastases. While chemotherapy, radiation therapy and targeted therapy can 53 extend overall survival, less than 15% of patients with metastatic CRC survive 54 beyond 5 years [3]. Therefore, the novel and more effective therapeutic approaches 55 for CRC are necessary to develop. 56 In the recent years, based on a better knowledge of the complex interactions 57 between the immune system and the tumor microenvironment, immunotherapy has 58 become a novel effective and promising therapeutic strategy for cancer, and its 59 efficacy was widely tested by CRC model. The vast majority of CRC patients with 60 deficient mismatch repair (dMMR) or highly microsatellite instable (MSI-H) benefit 61 from immune checkpoint inhibitors, which is not effective in other CRC patients with 62 proficient MMR (pMMR) or microsatellite stable (MSS) [4]. Patients with CRC do 63 not respond to autologous tumour lysate DC (ADC) and peptide vaccines [4]. T cells, 64 which are engineered to express an affinity-enhanced T-cell rece...

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Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer

et al. 2021

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Immunotherapy of colorectal cancer: Challenges for therapeutic efficacy

Cited by 238 publications

References 117 publications

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic

Cetuximab Rechallenge Plus Avelumab in Pretreated Patients With RAS Wild-type Metastatic Colorectal Cancer

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