Prognostic impact of immune-microenvironment in colorectal liver metastases resected after triplets plus a biologic agent: A pooled analysis of five prospective trials

Moretto, Roberto; Corallo, Salvatore; Belfiore, Antonino; Rossini, Daniele; Boccaccino, Alessandra; Centonze, Giovanni; Morano, Federica; Germani, Marco Maria; Loupakis, Fotios; Morelli, Luca; Urbani, Lucio; Brich, Silvia; Marmorino, Federica; Prisciandaro, Michele; Aprile, Giuseppe; Fassan, Matteo; Cillo, U.; Cattaneo, Laura; Fontanini, Gabriella; Braud, Filippo de; Falcone, Alfredo; Milione, Massimo; Pietrantonio, Filippo; Cremolini, Chiara

doi:10.1016/j.ejca.2020.04.045

Cited by 19 publications

(11 citation statements)

References 39 publications

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“…Effect of chemotherapy on the immune infiltrate was described in nonmetastatic rectal cancer, with an increased stromal CD8 high and CD4 T cells after chemoradiotherapy, associated with a better prognosis [ 44 ]. Recently, the pooled analysis of postchemotherapy resected metastases of pMMR CRC confirmed the good prognosis of patients with such an inflamed microenvironment [ 23 ]. However, this analysis did not include paired tumors before and after treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In the pMMR cohort of the NICHE study, the presence of T cells with co‐expression of CD8 and PD‐1 was the only biomarker found to predict major or partial pathological response [ 19 ]. Data regarding the expression of PD‐L1 in CRC liver metastases and notably the interactions of PD‐L1 with elements of the immune tumor microenvironment, as well as patient outcome, have recently been described [ 23 ]. No correlation between tumor‐specific PD‐L1 expression and survival was shown, confirming the results from other studies [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

et al. 2022

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In the era of immune checkpoint inhibitors, understanding the metastatic microenvironment of proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) is of paramount importance to both prognostication and the development of more effective novel therapies. In this study, primary and paired metastasis tissue samples were collected from patients with resectable metastatic CRC treated with adjuvant FOLFOX or peri‐operative chemotherapy in the MIROX phase III prospective study. In total, 74 cancer tissues were stained for CD3, CD8, Forkhead box protein 3 (FOXP3), programmed cell death protein‐1 (PD‐1, invasive front, stromal, intra‐epithelial compartments), and programmed death‐ligand 1 (PD‐L1, tumor, immune cells). The immune profiling of primary CRC had a limited value to predict the immune context of paired metastases for all markers but CD3+. The expression of CD8 and PD‐L1 was higher in metastases after neoadjuvant FOLFOX. In metastases, both CD3 T cells at the invasive front and PD‐L1 expressions on immune cells were predictive of better disease‐free survival. These results show that the effect of FOLFOX on modifying the immune microenvironment in resected CRC metastases and measurement of PD‐L1 expression and tumor‐infiltrating CD8 T cells in pMMR/MSS metastatic tissue samples could improve treatment strategies of metastatic CRC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

et al. 2022

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“…In this study, ORR was markedly higher in group A than in B group because the combination of irinotecan and capecitabine exerted enhanced efficiency in antitumor effect. Irinotecan impairs the synthesis of tumor cell nucleic acid, while capecitabine slows down the recombination of tumor cell nucleic acid [15][16][17]. Therefore, the lesions disappeared faster in group A.…”

Section: Discussionmentioning

confidence: 99%

Effect of capecitabine combined with irinotecan on the safety of colon cancer treatment, patients’ adverse reactions and quality of life

Fan¹,

Li²,

Zhong³

et al. 2021

Trop. J. Pharm Res

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Purpose: To study the impact of the combination of capecitabine and irinotecan on the safety of colon cancer treatment, adverse reactions and wellbeing of patients.Methods: Colon cancer subjects (n =120) admitted to Guangzhou First People’s Hospital, Guangzhou, China were assigned equally to two groups (A and B) according to their order of admission, and they received intravenous infusion of irinotecan. In addition, group A patients were administered capecitabine, but those in B group were given tegafur, gimeracil and oteracil porassium. The patients in groups A and B were compared with respect to the incidence of unwanted effects, quality of life (QoL), and overall clinical efficacy of the treatments.Results: Cases of nausea and vomiting, delayed diarrhea and sensory neuropathy of the patients were significantly reduced in group A, relative to group B. Moreover, QoL score after treatment was markedly higher in group A than in group B, while the objective response rate (ORR) of colon cancer patients in group A was also significantly higher than that in group B (p < 0.05). However, no obvious difference in disease control rate (DCR) was observed between groups A and B (p > 0.05).Conclusion: Combined capecitabine and irinotecan therapy effectively improves clinical prognosis, reduces the incidence of adverse reactions, and is safe in colon cancer patients. Therefore, the combined treatment may be beneficial in the management of colon cancer.

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“…In a retrospective analysis of immunological parameters assessed on CRC liver metastases resected after pre-operative intensified chemotherapy plus bevacizumab or cetuximab, TME-driven immune response was associated with better survival regardless of other well-known prognostic factors. The intensified chemotherapy regimen may contribute to the activation of the immune phenotype, thus supporting the combination of immunotherapy with FOLFOXIRI in first-line therapy in order to establish a favorable TME for immunotherapy action [76].…”

Section: Anti-vegf and Chemotherapy + Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immune Checkpoint Inhibitors in pMMR Metastatic Colorectal Cancer: A Tough Challenge

Marmorino

Boccaccino

Germani

et al. 2020

Cancers

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The introduction of checkpoint inhibitors provided remarkable achievements in several solid tumors but only 5% of metastatic colorectal cancer (mCRC) patients, i.e., those with bearing microsatellite instable (MSI-high)/deficient DNA mismatch repair (dMMR) tumors, benefit from this approach. The favorable effect of immunotherapy in these patients has been postulated to be due to an increase in neoantigens due to their higher somatic mutational load, also associated with an abundant infiltration of immune cells in tumor microenvironment (TME). While in patients with dMMR tumors checkpoint inhibitors allow achieving durable response with dramatic survival improvement, current results in patients with microsatellite stable (MSS or MSI-low)/proficient DNA mismatch repair (pMMR) tumors are disappointing. These tumors show low mutational load and absence of “immune-competent” TME, and are intrinsically resistant to immune checkpoint inhibitors. Modifying the interplay among cancer cells, TME and host immune system is the aim of multiple lines of research in order to enhance the immunogenicity of pMMR mCRC, and exploit immunotherapy also in this field. Here, we focus on the rationale behind ongoing clinical trials aiming at extending the efficacy of immunotherapy beyond the MSI-high/dMMR subgroup with particular regard to academic no-profit studies.

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Prognostic impact of immune-microenvironment in colorectal liver metastases resected after triplets plus a biologic agent: A pooled analysis of five prospective trials

Cited by 19 publications

References 39 publications

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

Immune microenvironment in patients with mismatch‐repair‐proficient oligometastatic colorectal cancer exposed to chemotherapy: the randomized MIROX GERCOR cohort study

Effect of capecitabine combined with irinotecan on the safety of colon cancer treatment, patients’ adverse reactions and quality of life

Immune Checkpoint Inhibitors in pMMR Metastatic Colorectal Cancer: A Tough Challenge

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