The “Immunoscore” in rectal cancer: could we search quality beyond quantity of life?

Kirilovsky, Amos; Sissy, Carine El; Zeitoun, Guy; Marliot, Florence; Haicheur, Nacilla; Lagorce-Pagès, Christine; Taı̈eb, Julien; Karoui, Mehdi; Custers, Petra; Dizdarevic, Edina; Iseas, Soledad; Hansen, Torben Frøstrup; Jensen, Lars Henrik; Beets, Geerard L.; Gérard, Jean Pierre; Castillo-Martin, Mireia; Figueiredo, Nuno; Habr‐Gama, Angelita; Perez, Rodrigo Oliva; Galon, Jérôme; Pagès, Franck

doi:10.18632/oncotarget.28100

Cited by 5 publications

(3 citation statements)

References 111 publications

(129 reference statements)

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“… 35 , 39 , 41 , 42 A biopsy-adapted IS could possibly even aid with predicting therapy response in rectal cancer patients. 43 , 44 Together with our observation, that hyperplasia of the LN paracortex (also known as a T-cell zone) relates to prolonged survival, this underlines that the host antitumor response probably is more than a local response and LNs play an important in the immunological reaction to the tumor.…”

Section: Discussionsupporting

confidence: 57%

The Role of Nonmetastatic Lymph Nodes in the Survival of Colorectal Cancer: A Systematic Review

Pennings,

van der Velden,

Kloft

et al. 2023

Annals of Surgery Open

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Objective: In this review, we aim to provide an overview of literature on lymph node (LN) histomorphological features and their relationship with the prognosis in colorectal cancer (CRC). Background: Lymph nodes play a crucial role in the treatment and prognosis of CRC. The presence of LN metastases considerably worsens the prognosis in CRC patients. Literature has shown that the total number of LNs and the number negative LNs (LNnegs) has prognostic value in CRC patients. In esophageal carcinoma, LN size seems to be surrogate of the host antitumor response and a potentially clinically useful new prognostic biomarker for (y)pN0 esophageal carcinoma. Methods: A comprehensive search was performed in Pubmed, Embase, Medline, CINAHL, and the Cochrane library in March 2021. The PRISMA guidelines were followed. Only studies focusing on histomorphological features and LN size and their relation to overall survival were selected. Results: A total of 9 unique articles met all inclusion criteria and were therefore included in this systematic review. Six of these studies investigated HMF (eg, paracortical hyperplasia, germinal center predominance, and sinus histiocytosis) and 4 studies LNneg size and their relationship with overall survival. The presence of paracortical hyperplasia and an increased number of large LNnegs is related to a more favorable prognosis in CRC. Conclusion: The results of this systematic review seem to support the hypothesis that there is a relationship between the host antitumor response reflected in different histomorphological reaction patterns visible in LNnegs and LNneg size related to survival in CRC patients.

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Section: Discussionsupporting

confidence: 57%

The Role of Nonmetastatic Lymph Nodes in the Survival of Colorectal Cancer: A Systematic Review

Pennings,

van der Velden,

Kloft

et al. 2023

Annals of Surgery Open

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“…In the recent RAPIDO trial 37 , the experimental TNT group increased the rate of pCR and decreased the rate of distant metastases compared to the conventional approach. On the other hand, some studies have shown that an “immunoscore” 38 , calculated with counts of CD8+ or FoxP3+ regulatory T cells, outperformed the traditional TNM staging in predicting outcomes in CCR 39 and a plethora of immune checkpoint inhibitors and other immunotherapies are emerging 40 . Therefore, it seems relevant to assess the impact of inflammatory markers in the subtyping of disease to select the best strategy for each patient.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-neutrophil (PN) index in locally advanced rectal cancer patients: a retrospective cohort study

Morais,

Fonseca,

Machado-Neves

et al. 2024

Annals of Medicine &Amp; Surgery

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Introduction: In locally advanced rectal cancers (LARC), TNM staging is far from optimal. We aimed to investigate the value of previously described circulating biomarkers as predictors of prognosis. Methods: Retrospective analysis of 245 LARC patients diagnosed between January 2010 and December 2022, who underwent neoadjuvant chemoradiotherapy and surgery at two centers. A Cox regression and Kaplan-Meier analysis were performed. Results: Posttreatment platelet-to-lymphocyte ratio (PLR) predicted pCR. Neutrophil-to-lymphocyte ratio (NLR) in two timepoints of the treatment significantly predicted overall survival, whereas platelet-neutrophil (PN) index significantly predicted disease-free survival. In pathological stage II, PN index predicted patients of higher risk of disease-free survival. Conclusion: Blood parameters might allow the definition of subgroups of risk, beyond TNM, for the application of different therapeutic strategies.

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“…As shown in Figure 5 , these findings can explain why women have a better outcome than male patients with rectal cancer and are particularly relevant since several trials are now ongoing testing immune checkpoint inhibitors in CRC, calling for reliable predictors of therapy response 36 . Moreover, the analysis of TME has been proposed to predict response to chemotherapy in CRC patients, and the immunoscore is currently being tested as a potential predictor of response to neoadjuvant chemoradiotherapy in LARC 37 . Based on the results of our study and as proposed by other authors 6 , sex should be considered when defining the treatment strategy of rectal cancer patients or designing prognostic scores, acknowledging the significant differences in epidemiology, cancer biology, and response to therapy.…”

Section: Discussionmentioning

confidence: 99%

IMMUNOREACT 5: female patients with rectal cancer have better immune editing mechanisms than male patients – a cohort study

Spolverato

Fassan

Capelli

et al. 2023

International Journal of Surgery

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Background: Studies evaluating sex differences in colorectal cancer (CRC) tumor microenvironment are limited, and no previous study has focused on rectal cancer patients’ constitutive immune surveillance mechanisms. The authors aimed to assess gender-related differences in the immune microenvironment of rectal cancer patients. Methods: A systematic review and meta-analysis were conducted up to 31 May 2021, including studies focusing on gender-related differences in the CRC tumor microenvironment. Data on the mutational profile of rectal cancer were extracted from the Cancer Genome Atlas (TCGA). A subanalysis of the two IMMUNOREACT trials (NCT04915326 and NCT04917263) was performed, aiming to detect gender-related differences in the immune microenvironment of the healthy mucosa in patients with early (IMMUNOREACT 1 cohort) and locally advanced rectal cancer following neoadjuvant therapy (IMMUNOREACT 2 cohort). In the retrospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 442 patients (177 female and 265 male), while in the retrospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), we enrolled 264 patients (80 female and 184 male). In the prospective IMMUNOREACT 1 cohort (therapy naive), the authors enrolled 72 patients (26 female and 46 male), while in the prospective IMMUNOREACT 2 cohort (patients who had neoadjuvant therapy), the authors enrolled 105 patients (42 female and 63 male). Results: Seven studies reported PD-L1 expression in the CRC microenvironment, but no significant difference could be identified between the sexes. In the TGCA series, mutations of SYNE1 and RYR2 were significantly more frequent in male patients with rectal cancer. In the IMMUNOREACT 1 cohort, male patients had a higher expression of epithelial cells expressing HLA class I, while female patients had a higher number of activated CD4+Th1 cells. Female patients in the IMMUNOREACT 2 cohort showed a higher infiltration of epithelial cells expressing CD86 and activated cytotoxic T cells (P=0.01). Conclusions: Male patients have more frequent oncogene mutations associated with a lower expression of T-cell activation genes. In the healthy mucosa of female patients, more Th1 cells and cytotoxic T cells suggest a potentially better immune response to the tumor. Sex should be considered when defining the treatment strategy for rectal cancer patients or designing prognostic scores.

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The “Immunoscore” in rectal cancer: could we search quality beyond quantity of life?

Cited by 5 publications

References 111 publications

The Role of Nonmetastatic Lymph Nodes in the Survival of Colorectal Cancer: A Systematic Review

The Role of Nonmetastatic Lymph Nodes in the Survival of Colorectal Cancer: A Systematic Review

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-neutrophil (PN) index in locally advanced rectal cancer patients: a retrospective cohort study

IMMUNOREACT 5: female patients with rectal cancer have better immune editing mechanisms than male patients – a cohort study

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