Inhibition of host Ogr1 enhances effector CD8+ T-cell function by modulating acidic microenvironment
Authors: Haizeng Zhang
Chuan Qin
Xingjiu Yang
Ran Gao
Lin Cao
Weisha Li
Wenlong Zhang
Mengyuan Li
Xiaohong Chen
Journal: Cancer Gene Therapy (2021)
Discipline: CLINICAL MEDICINE
Keywords: Immunotherapy; Cancer; Immune checkpoint blockade; Adoptive T-cell transfer; Acidic microenvironment
Affiliations: Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China., NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China., National Cancer Center/Cancer Hospital, CAMS & PUMC, Beijing, China., Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. ., NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China. .

Abstract:  Immunotherapies for cancer, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to a long-lasting clinical response. But the therapeutic response rate remains low on account of many tumors that have evolved sophisticated strategies to evade immune surveillance. Solid tumors are characterized by the highly acidic microenvironment, which may weaken the effectiveness of antitumor immunity. Here, we explored a promising therapeutic development deployed by pH manipulation for avoiding immunoevasion. The highly acidified microenvironment of melanoma induces the expression of G-protein-coupled receptor (Ogr1) in T cells, which weakened their effective function and promote tumor growth. Ogr1 inhibition reactivate CD8+ T cells and have a cytotoxic role by reducing the activity of high glycolysis, resulting in comparatively low acidification of the tumor microenvironment, and leads to tumor suppression. In addition, the adoptive transfer of Ogr1-/--CD8+ T cells enhanced the antitumor responses, with the potential for immediate clinical transformation. 

Retracted: No

PubPeer comments:
 As per figure 4 of this paper - the purported machine learning application DOC3 is actually a four question quiz program I have functionally recreated the program in figure four in the AutoIt scripting language (Windows computers only) for those curious below: Local $iAnswer = MsgBox(4,  AiSLDr , Do you have the following symptom: intense_cough_lasting_more_than_3_wee ) If $iAnswer = 7 Then MsgBox(8192,  ! ,  Program terminated ) EndIf Local $iAnswer = MsgBox(4,  AiSLDr , Do you have the following symptom: feel_extreme_weakness? ) If $iAnswer = 7 Then MsgBox(8192,  ! ,  Program terminated ) EndIf Local $iAnswer = MsgBox(4,  AiSLDr , Do you have the following symptom: fever? ) If $iAnswer = 7 Then MsgBox(8192,  ! ,  Program terminated ) EndIf Local $iAnswer = MsgBox(4,  AiSLDr , Do you have the following symptom: weight_fall? ) If $iAnswer = 7 Then MsgBox(8192,  ! ,  Program terminated ) EndIf msgbox(0, AiSLDr ,  You are suffering from active_lung_TB ) There is also a program called DOC4 in this paper that I have not recreated but appears to be a more advanced quiz application that calculates probability ,