Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 300-309 http://medscipublisher.com/index.php/cge 304 The composition and functional state of the tumor microenvironment are influenced by multiple factors, including the composition of cytokines, interstitial components, and the presence of inhibitory molecules, etc. Currently, researchers are attempting to transform "cold" tumors into "hot" ones, for instance, by combining ICIs with other drugs that can promote immune cell infiltration or regulate the tumor microenvironment. This is expected to enhance the therapeutic effect. 4.3 Intestinal flora, genetic background and combined treatment strategies More and more studies have shown that external factors such as intestinal flora can significantly affect the therapeutic effect of ICIs. Certain bacterial species, such as Akmannibacterium mucilicum and some bifidobacteria, are associated with enhanced immune response and improved prognosis in patients after ICIs (Routy et al., 2018). On the contrary, the use of antibiotics or intestinal flora imbalance may weaken the effect of immunotherapy, indicating that the microbiome plays an important role in regulating the human immune system. The patient's genetic background and whether combined therapy is adopted will also affect the efficacy of immunotherapy. For example, differences in HLA genotypes and immune-related genes may affect antigen presentation and the intensity of immune response (Chowell et al., 2018; Liu and Zhang, 2025). In addition, the combination of ICIs with chemotherapy, targeted drugs or radiotherapy can change the immune status of tumors and may overcome the problem of drug resistance. However, these combination regimens may also bring more side effects, and the appropriate patients need to be carefully selected (Table 1) (Gandhi et al., 2018; Hellmann et al., 2019). Table 1 Treatment-Related Adverse Events in All the Recipients of Nivolumab plus Ipilimumab or Chemotherapy (Adopted from Hellmann et al., 2019) Adverse Event Nivolumab plus Ipilimumab (n=576) Chemotherapy (n=570) Any Grade Grade 3–4 Any Grade Grade 3–4 Number of patients (percent) Treatment-related adverse events All events 442 (76.7) 189 (32.8) 467 (81.9) 205 (36.0) Reported in ≥15% of patients Diarrhea 98 (17.0) 10 (1.7) 55 (9.6) 4 (0.7) Rash 98 (17.0) 9 (1.6) 30 (5.3) 0 Fatigue 83 (14.4) 10 (1.7) 108 (18.9) 8 (1.4) Decreased appetite 76 (13.2) 4 (0.7) 112 (19.6) 7 (1.2) Nausea 57 (9.9) 3 (0.5) 206 (36.1) 12 (2.1) Anemia 22 (3.8) 8 (1.4) 188 (33.0) 66 (11.6) Neutropenia 1 (0.2) 0 98 (17.2) 54 (9.5) Treatment-related serious adverse events 141 (24.5) 106 (18.4) 79 (13.9) 61 (10.7) Treatment-related adverse events leading to discontinuation† 104 (18.1) 71 (12.3) 52 (9.1) 28 (4.9) Treatment-related death‡ 8 (1.4) — 6 (1.1) — Table caption: The determination that an adverse event was related to a trial treatment was made by the investigators. The minimum follow-up for safety analyses was 28.3 months, except for treatment-related serious adverse events, which had a mini-mum follow-up of 29.3 months. All treatment-related adverse events and serious adverse events were reported during the time between the first dose of a trial treatment and 30 days after the last dose; † For nivolumab plus ipilimumab, these events included treatment-related adverse events leading to the discontinuation of ipilimumab alone or the discontinuation of both nivolumab and ipilimumab; the discontinuation of nivolumab alone was not permitted. Adverse events leading to the discontinuation of ipilimumab earlier than the discontinuation of nivolumab occurred in 18 patients (3.1%); ‡ Treatment-related deaths in the group that received nivolumab plus ipilimumab were from pneumonitis (in 4 patients) and from shock, myocarditis, acute tubular necrosis, and cardiac tamponade (in 1 patient each). Deaths in the chemo-therapy group were from sepsis (in 2 patients) and from febrile neutropenia with sepsis, multiple brain infarctions, in-terstitial lung disease, and thrombocytopenia (in 1 patient each) (Adopted from Hellmann et al., 2019)
RkJQdWJsaXNoZXIy MjQ4ODYzNA==