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. 2023 Jan 10;15(2):437.
doi: 10.3390/cancers15020437.

Paving the Path for Immune Enhancing Nutrition in Colon Cancer: Modulation of Tumor Microenvironment and Optimization of Outcomes and Costs

Maria Raffaella Ambrosio  1 , Luigi Spagnoli  1 , Bruno Perotti  2 , Federica Petrelli  1 , Saverio Caini  3 , Calogero Saieva  3 , Sofia Usai  4 , Matteo Bianchini  2 , Andrea Cavazzana  1 , Marco Arganini  2 , Andrea Amorosi  5
Affiliations

Paving the Path for Immune Enhancing Nutrition in Colon Cancer: Modulation of Tumor Microenvironment and Optimization of Outcomes and Costs

Maria Raffaella Ambrosio et al. Cancers (Basel). .

Abstract

Introduction: Published evidence suggests that immunonutrition has the potential to decrease postoperative complications and reduce length of stay in patients undergoing surgery for colorectal cancer. However, only a few studies have analyzed the effects of immunonutrition on tumor microenvironment and evaluated its prognostic impact.

Material and methods: This is a single center retrospective study enrolling 50 patients undergoing elective surgery for colorectal cancer managed with immunonutrition and 50 patients managed with standard nutrition for comparison. Tumor microenvironment was analyzed before (on the biopsy at the time of diagnosis) and after (on the matched surgical specimen) administration of immunonutrition. Immune function related indicators, including cytotoxic T-lymphocytes, helper T-cells, antigen presenting cells, natural killer cells, T-exhausted lymphocytes, T-regulatory cells, M1 and M2 tumor associated macrophages and PD-L1 expression were assessed by immunohistochemistry. For both groups, clinicopathological data were collected and a 5-year follow-up was available.

Results: We found that immunonutrition significantly activated the T-cell response against cancer, alter tumor microenvironment phenotype towards M2 polarization and inhibits the PD1/PD-L1 axis. A lower rate of postoperative complications and a shorter length of stay (p = 0.04) were observed in the immune nutrition group. Compared to standard nutrition group, patients managed wit immune nutrition showed a higher 5-year overall survival (p = 0.001). Finally, immune nutrition allowed to reduce the hospital care costs.

Conclusions: Immunonutrition modulates tumor microenvironment by improving immune function and could prolong survival in patients undergoing elective surgery for colorectal cancer. Further studies are needed to optimize IN protocols and confirm their prognostic impact.

Keywords: T-lymphocytes; colorectal cancer; immunonutrition; macrophages; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Length of hospital stay in IN and non-IN group according to surgical procedure (laparoscopy vs. laparotomy), box plot.
Figure 2
Figure 2
Length of hospital stay in IN and non-IN group according to surgical procedure (laparoscopy vs. laparotomy), scatter plot.
Figure 3
Figure 3
Modulation of lymphoid cells in the TME of patients receiving IN from biopsy to surgical specimen. (A), CTL; (B), TH; (C), APC; (D), NK.
Figure 4
Figure 4
Modulation of TME of patients receiving IN from biopsy to surgical specimen. (A), T-exh lymphocytes; (B), T-reg cells; (C), TAM; (D), PD-L1 expression.
Figure 5
Figure 5
Modulation of TME in IN patients. Lower levels of infiltrating CTL and TH in the biopsy (A) than in the surgical sample (B); M2 macrophages (C) reverted to M1 in surgical sample (D). Higher expression of PD-L1 (E) in biopsy than in operatory specimen (F). (A–F), immunohistochemistry: (A,B): CD4/CD8 double stain; (C,D): CD68; (E,F): PD-L1; Original magnification (O.M.): (A,C–F): 10×; (B): 4×.
Figure 6
Figure 6
Absence of TME modulation in non-IN patients. No changes in the lymphoid population between the biopsy (A) and the surgical specimen (B); preservation of TAM polarization in the biopsy (C) and in the surgical specimen (D). Higher PD-L1 expression in both neoplastic cells and TME in the biopsy (E) and in the surgical specimen (F). (A–F), immunohistochemistry: (A,B): CD4/CD8 double stain; (C,D): CD68; (E,F): PD-L1; O.M.: (A,C–F): 10×; (B): 4×.
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This research received no external funding.