The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Roles of Sociological Factors and Sex/Gender in CPI Efficacy
2.1. Race
2.2. Ageing
2.3. Sex/Gender
3. Influence of Lifestyle on Outcome of CPI
3.1. Smoking
3.2. Alcohol Consumption
3.3. Diet
3.4. Exercise
3.5. Circadian Rhythms
3.6. Psycho-Emotional Disturbances
4. Effect of Metabolic Disorders on CPI Treatment
4.1. Obesity
4.2. Diabetes
4.3. Hypertension
5. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Expression Profile | Modulators | Role in CPI Responsiveness | Predictive vs. Prognostic Value | Reference |
---|---|---|---|---|---|
PD-1 | TIL | PTEN, PI3K-Akt pathway, STAT3 | Inhibits T cell proliferation | Predictive and prognostic | [6,7] |
PD-L1 | Tumor cells Macrophage, stroma cel | MAPK and PI3K or Akt pathways | On interaction with PD-1 inhibits T cell proliferation | Predictive and prognostic | [8,9] |
TIM3 | CD4, CD8 memory T cells, DC, NK cells, monocytes | IL-2, TNF-α, IFN-γ | Promotes T cell dysfunction/exhaustion, Tim3+ Tregs correlated with metastasis disease | Prognostic | [10,11] |
LAG-3 | CD4, CD8 T cells, NK cells, Treg cells | IL-10 and TGF-β1 | Promotes Treg mediated suppression Inhibits effector T cell proliferation | Prognostic | [12,13] |
TIGIT | Tregs, TILs (CD8), DCs | IFN-γ and IL-17 | Suppresses anti-tumor immunity by dampening CD8 T cell function via Tregs | Prognostic | [14,15] |
CTLA | Tregs, CD4 T cells | IL-2, PI3K pathway, Bcl-XL | Mediates immunosuppressive signaling by blocking co stimulatory CD28 receptor, inhibits T cell activation | Predictive and prognostic | [16,17] |
Factor Influencing | Effect on Check Point Inhibitor Treatment | Mechanism Involved | Cancer Type | HR(CI), p-Value of CPI Response * | Reference |
---|---|---|---|---|---|
Sex/gender | No correlation | -- | Advanced Squamous-Cell Non-Small-Cell Lung Cancer | -- | [43] |
For anti CTLA treatment PFS longer in males | Men have high CD8 T cells expression | NSCLC | HR Male: 0.77 (95% CI 0.63–0.94), p = 0.012 HR Female:0.89 (95% CI 0.76–1.05) p = 0.16 | [60] | |
Longer survival in females for anti CTLA treatment | -- | Melanoma | HR Female: 0.80 (95% CI 0.68–0.94) p = 0.006 | [60] | |
No correlation | -- | Advanced gastric and gastroesophageal junction adenocarcinoma | -- | [61] | |
Race | AA have high response rate to Nivolumab | AA have higher mutational burden | Lung cancer | -- | [55] |
Ageing | Adverse effects in elders in melanoma | Not clear | Melanoma, Metastatic melanoma | -- | [62,63] |
No correlation | -- | NSCLC | -- | [64] | |
Elders have less toxicity of CPI therapy | Not clear | Melanoma, non-small cell lung cancer, and renal cell carcinoma | -- | [65,66] |
Factor Influencing | Effect on Check Point Inhibitor Treatment | Mechanism Involved | Cancer Type | HR(CI), p-Value of CPI Response * | Reference |
---|---|---|---|---|---|
Exercise | Improved response to immunotherapy | Exercise lowers the expression of PD-1 on T cells mobilizes more CD8 t cells | Blood cancer | -- | [94] |
Low symptom burden | Not clear | Metastatic melanoma | -- | [95] | |
Alcohol Consumption | Improved response to immunotherapy | High intratumoral T cell infiltrate, overexpression of PD-L1 in never drinkers | Oral squamous cell carcinoma | -- | [96] |
No significant correlation between alcohol consumption and PD-L1 expression | -- | Oral squamous cell carcinoma | HR 1.2 (95% CI 0.91–1.71) p = 0.15 | [97] | |
Diet | Enhanced immunotherapy effect | Enhanced anti-tumor capacity of TAM | Prostate and renal cell carcinoma | -- | [98] |
Gut microbiome modifies host immunity | Melanoma | -- | [99] | ||
High LAG-3 induced by IL-17 | Gastric cancer | -- | [100] | ||
Smoking | Controversial reports in HNSC and LUSC | Increased mutation rate. Decreased immune cell infiltration and poorer survival in HNSC, reverse in LUSC | head and neck (HNSC) and lung (LUSC) squamous cell carcinoma | LUSC: HR 1.02 (95% CI 0.71–1.46) p = 0.92 | [101] |
High responsiveness | High mutation rate | Lung adenocarcinoma, NSCLC | NSCLC: HR 0.86(p = 0.61) | [58] | |
NSCLC: HR 0.81 (95% CI 0.27–2.43) p = 0.71 | [102] | ||||
NSCLC: HR 0.45 (95% CI 0.22–0.92) p = 0.02 | [103] | ||||
NSCLC: HR 0.71 (95% CI 0.63–0.82) p < 0.00001 | [104] | ||||
NSCLC: HR 0.15 (95% CI: 0.06–0.39) p = 0.0001 | [105] | ||||
Circadian rhythms | No direct evidence | Decreased Bimal-1 causes high PD-L1 expression | Not reported in cancer condition | -- | [106] |
Psyco-emotional changes | No direct evidence | Depression and stress decreases proliferation, increases apoptosis in T cells | Not reported in cancer condition | -- | [107] |
Factor Influencing | Effect on Check Point Inhibitor Treatment | Mechanism Involved | Cancer Type | Reference |
---|---|---|---|---|
Obesity | Improved survival | Not clear | Melanoma | [181] |
High response rate | Leptin in obesity cases promoted PD-1 expression on T cells | Melanoma, colorectal cancer | [13,129] | |
Acute limiting toxicity (ALT) | Low distribution of drug, high exposure | Melanoma | [182] | |
Worst Survival | Lower creatinine levels in obese females | Melanoma | [183] | |
Diabetes | Diabetes is secondary to immunotherapy | Endocrine toxicity, beta cell destruction | NSCLC Melanoma | [184,185,186,187] |
Hypertension | Secondary to immunotherapy | Inhibition of blood vessel formation | Colorectal cancer, Melanoma, Endometrial cancer | [188,189,190,191] |
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Deshpande, R.P.; Sharma, S.; Watabe, K. The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors. Cancers 2020, 12, 2983. https://doi.org/10.3390/cancers12102983
Deshpande RP, Sharma S, Watabe K. The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors. Cancers. 2020; 12(10):2983. https://doi.org/10.3390/cancers12102983
Chicago/Turabian StyleDeshpande, Ravindra Pramod, Sambad Sharma, and Kounosuke Watabe. 2020. "The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors" Cancers 12, no. 10: 2983. https://doi.org/10.3390/cancers12102983
APA StyleDeshpande, R. P., Sharma, S., & Watabe, K. (2020). The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors. Cancers, 12(10), 2983. https://doi.org/10.3390/cancers12102983