As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy. Such interrogation of the tumor, blood, and host immune parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. To approach these opportunities for progress, the Society for Immunotherapy of Cancer (SITC) reconvened the Immune Biomarkers Task Force. Comprised of an international multidisciplinary panel of experts, Working Group 4 sought to make recommendations that focus on the complexity of the tumor microenvironment, with its diversity of immune genes, proteins, cells, and pathways naturally present at baseline and in circulation, and novel tools to aid in such broad analyses.

https://jitc.bmj.com/content/jitc/5/1/44.full.pdf

Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy.

Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation.

Activation of the humoral immune system is initiated when antibodies recognize an antigen and trigger effector functions through the interaction with Fc engaging molecules. The most abundant immunoglobulin isotype in serum is Immunoglobulin G (IgG), which is involved in many humoral immune responses, strongly interacting with effector molecules. The IgG subclass, allotype, and glycosylation pattern, among other factors, determine the interaction strength of the IgG-Fc domain with these Fc engaging molecules, and thereby the potential strength of their effector potential. The molecules responsible for the effector phase include the classical IgG-Fc receptors (FcγR), the neonatal Fc-receptor (FcRn), the Tripartite motif-containing protein 21 (TRIM21), the first component of the classical complement cascade (C1), and possibly, the Fc-receptor-like receptors (FcRL4/5). Here we provide an overview of the interactions of IgG with effector molecules and discuss how natural variation on the antibody and effector molecule side shapes the biological activities of antibodies. The increasing knowledge on the Fc-mediated effector functions of antibodies drives the development of better therapeutic antibodies for cancer immunotherapy or treatment of autoimmune diseases.

The Ligands for Human IgG and Their Effector Functions

MicroRNAs (miRNAs) are short, noncoding, single-stranded RNA molecules that regulate gene expression at the post-transcriptional level by binding to mRNAs. miRNAs affect the course of processes of fundamental importance for the proper functioning of the organism. These processes include cell division, proliferation, differentiation, cell apoptosis and the formation of blood vessels. Altered expression of individual miRNAs has been shown in numerous cancers, which may indicate the oncogenic or suppressor potential of the molecules in question. This paper discusses the current knowledge about the possibility of using miRNA as a diagnostic marker and a potential target in modern anticancer therapies.

/pdf/mirnas-in-cancer-review-of-literature-3glxcili.pdf

miRNAs in Cancer (Review of Literature)

Beneficial and detrimental aspects of miRNAs as chief players in breast cancer: A comprehensive review.

Epidemiological studies have assessed the association between Fc gamma receptor IIIA (FCGR3A) 158 V/F and the response to rituximab-based therapy in patients with non-Hodgkin lymphoma (NHL), but the findings have been inconsistent. We performed this meta-analysis to obtain a better assessment of this relationship. Electronic database searches were conducted for relevant studies. A pooled odds ratio (OR) with a 95 % confidence interval (95 % CI) was used to assess the strength of the association. Analyses of the subgroup and publication bias were conducted. A total of 10 studies involving 1050 patients were analyzed. In all the genetic models, no clear relationship was found between the FCGR3A 158 V/F polymorphism and the response to rituximab-based therapy in NHL patients. When categorized by ethnicity, Asian individuals with the FCGR3A 158 V/V allele (OR = 4.37; 95 % CI = 1.07–17.73; P = 0.039) or the non-F/(FV + VV) (OR = 2.50; 95 % CI = 1.04–5.98; P = 0.040) allele have a significantly higher complete response rate (CR) compared to FF individuals. No obvious heterogeneities were observed. In addition, no statistical evidence for a publication bias was found. Our study suggested that the FCGR3A 158 V/F polymorphism can predict the treatment response to rituximab-based chemotherapy in NHL patients, especially for Asian individuals.

The FCGR3A polymorphism predicts the response to rituximab-based therapy in patients with non-Hodgkin lymphoma: a meta-analysis

MicroRNA-21 is an oncogenic miRNA that modulates the expression of multiple cancer-related target genes. We conducted this meta-analysis to assess diagnostic role of circulating miR-21 in CRC, hopi...

Diagnostic role of circulating MiR-21 in colorectal cancer: a update meta-analysis.

// Duo Liu 1, 2 , Nan Wu 1 , Haiming Sun 1 , Mei Dong 2 , Tianzhu Guo 3 , Peng Chi 4 , Guofu Li 5 , Donglin Sun 1 and Yan Jin 1 1 Department of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China 2 Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China 3 Department of Pharmacology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China 4 Department of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang, China 5 Department of Neurosurvery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China Correspondence to: Yan Jin, email: jinyan@ems.hrbmu.edu.cn Donglin Sun, email: sundl@ems.hrbmu.edu.cn Keywords: diffuse large B-cell lymphoma, rituximab, pharmacogenetic, prognosis Received: October 19, 2016      Accepted: March 09, 2017      Published: April 06, 2017 ABSTRACT The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes ( CD20 , FCGR2A , NAD(P)H, ABCC2 , ABCG2 and CYP3A5 ). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) ( P = 0.023) and event-free survival (EFS) ( P 60 years old) or male patients with ABCG2 rs2231137 GG genotype had poorer PFS and EFS than A allele. Moreover, CD20 rs2070770 CC and RAC2 rs13058338 AT genotypes were independent predictors of chemotherapy-induced toxicity. Cox proportional hazards analyses demonstrated that the GG genotype of ABCG2 rs2231137 and NCF4 rs1883112 were risk factors in DLBCL patients. In conclusion, the identified polymorphisms provide guide for the identification of DLBCL patients who are likely to benefit from chemotherapy.

/pdf/abcg2-and-ncf4-polymorphisms-are-associated-with-clinical-2o5tabufc9.pdf

ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.

To investigate whether cytokine genetic polymorphisms influence the outcome of diffuse large B cell lymphoma (DLBCL), we tested 337 consecutive DLBCL treated with CHOP or rituximab-CHOP (R-CHOP) from interleukin 10 (IL10), Bcl-2, and tumor necrosis factor (TNF)-α polymorphisms. Patients who carried the IL10 rs1800871 TT or rs1800872 AA genotype showed higher complete response (CR) and overall response rate (ORR) significantly. A longer progression-free survival (PFS) was observed in patients with IL10 rs1800871 TT (P = 0.017) or rs1800872 AA (P = 0.017) genotype after rituximab-based chemotherapy, and better PFS was also noted with Bcl-2 rs1801018 AA genotype in the CHOP group (P = 0.048). Furthermore, the R-CHOP group patients who carried the IL10 non-CCA haplotype had longer PFS (P = 0.030). Cox proportional hazards analyses demonstrated that the genotype TT of IL10 rs1800871 and AA plus AC of rs1800872 were predictive of longer PFS and event-free survival (EFS) in DLBCL patients treated with R-CHOP. And the Bcl-2 rs2279115 AA plus AC genotypes and rs1801018 GG genotype were risk factors for EFS in DLBCL patients treated with CHOP. In conclusion, the results reminded us those DLBCL patients with IL10 rs1800871 TT, rs1800872 AA, or IL10 non-CCA haplotype are likely to benefit from the therapy of rituximab-based chemotherapy.

Mei Dong

Papers

The FCGR3A polymorphism predicts the response to rituximab-based therapy in patients with non-Hodgkin lymphoma: a meta-analysis

Diagnostic role of circulating MiR-21 in colorectal cancer: a update meta-analysis.

ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP.

Polymorphisms in cytokine genes as prognostic markers in diffuse large B cell lymphoma patients treated with (R)-CHOP.