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Gastric cancer (GC) is the fifth most prevalent type of cancer worldwide. Gastric tumor cells express MICA protein, a ligand to NKG2D receptor that triggers natural killer (NK) cells effector functions for early tumor elimination. MICA gene is highly polymorphic, thus originating alleles that encode protein variants with a controversial role in cancer. The main goal of this work was to study MICA gene polymorphisms and their relationship with the susceptibility and prognosis of GC. Fifty patients with GC and 50 healthy volunteers were included in this study. MICA alleles were identified using Sanger sequencing methods. The analysis of MICA gene sequence revealed 13 MICA sequences and 5 MICA-short tandem repeats (STR) alleles in the studied cohorts We identified MICA * 002 ( * A9) as the most frequent allele in both, patients and controls, followed by MICA * 008 allele ( * A5.1). MICA * 009/049 allele was significantly associated with increased risk of GC (OR: 5.11 [95% CI: 1.39–18.74], p = 0.014). The analysis of MICA-STR alleles revealed a higher frequency of MICA * A5 in healthy individuals than GC patients (OR = 0.34 [95% CI: 0.12–0.98], p = 0.046). Survival analysis after gastrectomy showed that patients with MICA * 002/002 or MICA * 002/004 alleles had significantly higher survival rates than those patients bearing MICA * 002/008 ( p = 0.014) or MICA * 002/009 (MICA * 002/049) alleles ( p = 0.040). The presence of threonine in the position MICA-181 (MICA * 009/049 allele) was more frequent in GC patients than controls ( p = 0.023). Molecular analysis of MICA-181 showed that the presence of threonine provides greater mobility to the protein than arginine in the same position (MICA * 004), which could explain, at least in part, some immune evasion mechanisms developed by the tumor. In conclusion, our findings suggest that the study of MICA alleles is crucial to search for new therapeutic approaches and may be useful for the evaluation of risk and prognosis of GC and personalized therapy.

An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation. Humoral response to MICA antigens has repeatedly been associated with lower graft survival and an increased risk of acute and chronic rejection following kidney and liver transplantation with few studies showing conflicting results. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, a definitive consensus on this relationship has not been arrived yet. Furthermore, only a few studies have dealt with the impact of MICA donor-specific antibodies as compared to those that are not donor specific on graft outcome. In addition to the membrane bound form, a soluble isoform of MICA (sMICA), which has the potential to engage the natural killer cell-activating receptor NKG2D resulting in endocytosis and degradation of receptor-ligand interaction complex leading to suppression of NKG2D-mediated host innate immunity, has been a subject of intense discussion. Most studies on sMICA have been directed toward understanding their influence on tumor growth, with limited literature focusing its role in transplant biology. Furthermore, a unique dimorphism (methionine to valine) at position 129 in the α2 domain categorizes MICA alleles into strong (MICA-129 met) and weak (MICA-129 val) binders of NKG2D receptor depending on whether they have methionine or valine at this position. Although the implications of MICA 129 dimorphism have been highlighted in hematopoietic stem cell transplantation, its role in solid organ transplantation is yet to be explored. This review summarizes the currently available information on MICA antibodies, soluble MICA, and MICA-129 dimorphism in a setting of solid organ transplantation.

This paper aims to present an overview of MICA and natural killer group 2 member D (NKG2D) genetic and functional interactions and their impact on kidney transplant outcome. Organ transplantation has gone from what can accurately be called a \"clinical experiment\" to a routine and reliable practice, which has proven to be clinically relevant, life-saving and cost-effective when compared with non-transplantation management strategies of both chronic and acute end-stage organ failures. The kidney is the most frequently transplanted organ in the world (transplant-observatory). The two treatment options for end-stage renal disease (ESRD) are dialysis and/or transplantation. Compared with dialysis, transplantation is associated with significant improvements in quality of life and overall longevity. A strong relationship exists between allograft loss and human leukocyte antigens (HLA) antibodies (Abs). HLA Abs are not the only factor involved in graft loss, as multiple studies have shown that non-HLA antigens are also involved, even when a patient has a good HLA matche and receives standard immunosuppressive therapy. A deeper understanding of other biomarkers is therefore important, as it is likely to lead to better monitoring (and consequent success) of organ transplants. The objective is to fill the void left by extensive reviews that do not often dive this deep into the importance of MICA and NKG2D in allograft acceptance and their partnership in the immune response. There are few papers that explore the relationship between these two protagonists when it comes to kidney transplantation. This is especially true for the role of NKG2D in kidney transplantation. These reasons give a special importance to this review, which aims to be a helpful tool in the hands of researchers in this field.