Body mass index, adiposity and tumour infiltrating lymphocytes as prognostic biomarkers in patients treated with immunotherapy: A multi-parametric analysis

Espósito, Angela; Marra, Antonio; Bagnardi, Vincenzo; Frassoni, Samuele; Morganti, Stefania; Viale, Giulia; Zagami, Paola; Varano, Gianluca Maria; Buccimazza, Giorgio; Orsi, Franco; Venetis, Konstantinos; Mazzarella, Luca; Fusco, Nicola; Curigliano, Giuseppe

doi:10.1016/j.ejca.2020.12.028

Cited by 18 publications

(20 citation statements)

References 37 publications

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“…In fact, in patients with metastatic solid cancers, both SAT and visceral adipose tissue measured by CT-scan at lumbar 3 vertebra were not associated with overall survival [32]. This lack of association was confirmed by Wang et al in metastatic renal cancer who received immunotherapy [33].…”

Section: Clinical Impact Of Adipose Tissue Wasting In Cachexiamentioning

confidence: 85%

Metabolic and histomorphological changes of adipose tissue in cachexia

Molfino

Imbimbo

Muscaritoli

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewTo describe the role of the main changes occurring in adipose tissue during cachexia and how these affects patient's outcomes, with a specific focus on cancer.Recent findingsIn cachexia, the changes within the adipose tissue have been recently described as the presence of inflammatory infiltration (T-lymphocytes and macrophages), enhanced fibrosis, and the occurrence of beige adipocytes (i.e., browning). The latter one is a process driving cachexia enhancing thermogenesis, primarily via modulation of uncoupling protein 1. Also, increased lipolysis of white adipose tissue, especially in cancer, via higher expression of hormone sensible and adipose tissue triglyceride lipases, was detected in experimental models and in human adipose tissue. Other systemic metabolic alterations occur in association with changes in adiposity, including insulin resistance and increased inflammation, all conditions associated with a worse outcome. Moreover, these profound metabolic alterations were shown to be implicated in several consequences, including extreme and progressive unvoluntary body weight loss.SummaryAlterations in adiposity occur early during cachexia. Adipose tissue atrophy, as well as metabolic changes of white adipose tissues were observed to be pivotal in cachexia, and to be implicated in several clinical complications and poor prognosis.Further research is necessary to clarify the mechanisms underlying the loss of adiposity and therefore to identify novel therapeutic options to counteract this phenomenon in cachexia.

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Section: Clinical Impact Of Adipose Tissue Wasting In Cachexiamentioning

confidence: 85%

Metabolic and histomorphological changes of adipose tissue in cachexia

Molfino

Imbimbo

Muscaritoli

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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“…However, in recent years, immunotherapy has been clinically used for various carcinomas. Among them, there are some reports that the therapeutic effect is high in obese patients [ 60 – 62 ]. It is also reported that the relationship between BMI and therapeutic effect is contradictory between cell-mediated antineoplastic agents and immunotherapy [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy

et al. 2021

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Purpose The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. Methods The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and < 30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014. Results The median BMI was 21.9 kg/m2 (range, 14.3–38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031). Conclusions Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

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“…Emerging evidence also supports the utility of body fat measurement by computed imaging in studying the efficacy of ICI therapy in cancer patients [ 28 , 29 , 30 , 31 ]. Notably, higher SFA, VFA/SFA (V/S) ratio, and TFA among advanced cancer patients treated with ICIs were associated with increased OS and PFS [ 28 , 30 , 32 ]. Meanwhile, VFA was found not to have an effect on OS and PFS in a sample of non-small cell lung cancer patients on ICIs [ 31 ].…”

Section: Introductionmentioning

confidence: 93%

“…There are established quantitative measures of intra-abdominal fat volume, such as visceral fat area (VFA), subcutaneous fat area (SFA), and total fat area (TFA: sum of VFA and SFA), which can be obtained from computed tomography (CT) imaging and used to evaluate obesity and obesity-related risks [25][26][27]. Emerging evidence also supports the utility of body fat measurement by computed imaging in studying the efficacy of ICI therapy in cancer patients [28][29][30][31]. Notably, higher SFA, VFA/SFA (V/S) ratio, and TFA among advanced cancer patients treated with ICIs were associated with increased OS and PFS [28,30,32].…”

Section: Introductionmentioning

confidence: 99%

Obesity Measured via Body Mass Index May Be Associated with Increased Incidence but Not Worse Outcomes of Immune-Mediated Diarrhea and Colitis

Kono

Shatila

et al. 2023

Cancers

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Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3–4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.

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Body mass index, adiposity and tumour infiltrating lymphocytes as prognostic biomarkers in patients treated with immunotherapy: A multi-parametric analysis

Cited by 18 publications

References 37 publications

Metabolic and histomorphological changes of adipose tissue in cachexia

Metabolic and histomorphological changes of adipose tissue in cachexia

Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy

Obesity Measured via Body Mass Index May Be Associated with Increased Incidence but Not Worse Outcomes of Immune-Mediated Diarrhea and Colitis

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