## 6 The Influence of Diet and Probiotics on the Response to Immunotherapy  
Various studies are currently being conducted to evaluate the efficacy of dietary interventions or microbiome modification in patients who have received immunotherapeutic \begin{table}
\begin{tabular}{c c c c} \hline
**Immune Checkpoint** & **Immunoglobulin** & **Target** & **Treatment of Different Tumours** \\
**Inhibitors** & **Type** & **Molecule** & **Treatment of Different Tumours** \\ \hline Ipilimumab (MDX-010) & IgG-1x & CTLA-4 & \begin{tabular}{c} Advanced melanoma \\ Advanced renal cancer \\ \end{tabular} \\ \hline Pembrolizumab (MK-3475) & IgG-4x & PD-1 & \begin{tabular}{c} Advanced melanoma and adjuvant \\ Metastatic non-small cell lung cancer \\ Advanced bladder cancer \\ \end{tabular} \\ \hline Nivolumab (MDX-1106) & IgG4 & PD-1 & \begin{tabular}{c} Advanced melanoma and adjuvant \\ Metastatic non-small cell lung cancer \\ Advanced bladder cancer \\ \end{tabular} \\ \hline Cemiplimab (L01 XC33) & IgG4 & PD-1 & Cutaneous Squamous Cell Carcinoma \\ \hline Atezolizumab (MPDL3280A) & IgG1 & PD-L1 & \
\begin{tabular}{c} Advanced bladder cancer \\ Metastatic non-small cell lung cancer \\ \end{tabular} \\ \hline Durvalumab (MEDI4736) & IgG1 & PD-L1 &
\begin{tabular}{c} Locally advanced unresectable \\ non-small cell lung cancer \\ \end{tabular} \\ \hline Avelumab (MSB0010718C) & IgG1 & PD-L1 & Metastatic Merkel cell carcinoma \\ \hline \end{tabular}
\end{table} 
Table 2: ICIs currently approved by the European Medicines Agency (EMA) in the treatment of solid tumours. Different examples of your current indications are shown in the right column. treatment [50]. Most clinical trials in this domain have involved faecal microbiota transplantation, with smaller trials using probiotics or diets rich in fibre and low in fat. Especially relevant is the study NCT03700437, which evaluated the efficacy of a dietary treatment 72 h before and 24 h after the administration of chemo- and immunotherapy (carboplatin plus pemetrexed plus pembrolizumab) in patients who had a lung adenocarcinoma. Another relevant study is NCT03950635, on patients who had a history of melanoma and who did not have tumour disease. In these patients, the effects of a dietary intervention were evaluated for two groups: the first group was on a diet rich in fibre and the second group on a ketogenic diet [51]. These studies allow us to evaluate the direct effects of a dietary intervention both in diseased patients undergoing an immunotherapeutic treatment and in patients who have highly immunogenic tumours (e.g., melanoma) without tumour disease. The main studies are found in Table 3.  
Studies have shown how a dietary intervention led to changes in the microbiome in the first five days of the diet [52]. Diets that include fibre, as previously stated, produce beneficial changes in the gut microbiota for the maintenance of homeostasis. A recent study showed that 46 patients who were treated with anti-PD1, underwent a dietary intervention, and received probiotics (a high-fibre diet) were five times more likely to respond to immunotherapeutic treatment than those on low-fibre diets [50]. Diets that contain a large amount of fibre and few calories increase the number of species of bacteria that are responsible for digesting and secreting mucin in the intestinal epithelium (_Akkermanasia municipalities, Bifidobacterium lungoun_, or _Faecalibacterium prausnitzii_), which are responsible for maintaining the epithelial barrier and therefore for increasing the effectiveness of ICIs. According to several studies, the abundance of these bacteria in the microbiome correlates to the consumption of a high-fibre diet [53]. Likewise, the increase in the number of bacteria of the species _Bacteroides fragilis_ that occurs by following a diet rich in fibre can induce the expression of IL-10, which prevents the expansion of Th17 lymphocytes, the damage to the intestinal mucosa that this would cause, and, in turn, the deregulation of the immune system and the least response to ICIs [54].