Function Of Heat Shock Proteins Research Articles

Characterization of HSP70 and HSP90 Gene Family in Takifugu fasciatus and Their Expression Profiles on Biotic and Abiotic Stresses Response.

Heat shock proteins (HSPs) play crucial roles in response to temperature changes and biotic stresses. However, the HSP gene family in the pufferfish (Takifugu fasciatus) herring has not been comprehensively investigated. This study presents a systematic analysis of the HSP70 and HSP90 gene families in T. fasciatus, focusing on gene characterization, conserved structural domains, molecular evolutionary history, and expression patterns of the HSP gene family under stress conditions. The findings reveal that 16 HSP genes are evolutionarily conserved, while hspa4 and hsp90aa appear specific to teleost fish. HSP genes exhibit widespread expression across 11 examined tissues, with most demonstrating high expression levels in the heart, brain, and liver. Furthermore, T. fasciatus was subjected to cryogenic and biotic stresses, revealing distinct expression patterns of HSPs under various stress conditions. The response of HSPs to cold stress and Aeromonas hydrophila infection was sustained. In contrast, gene expression of HSPs significantly changed only in the pre-infection period following Ichthyophthirius multifiliis infection, gradually returning to normal levels in the later stages. These experimental results provide a foundation for further in-depth investigations into the characteristics and functions of HSPs in T. fasciatus.

Heat shock responsive genes in Brassicaceae: genome-wide identification, phylogeny, and evolutionary associations within and between genera.

Heat stress affects the growth and development of Brassicaceae crops. Plant breeders aim to mitigate the effects of heat stress by selecting for heat stress tolerance, but the genes responsible for heat stress in Brassicaceae remain largely unknown. During heat stress, heat shock proteins (HSPs) function as molecular chaperones to aid in protein folding, and heat shock transcription factors (HSFs) serve as transcriptional regulators of HSP expression. We identified 5002 heat shock related genes, including HSPs and HSFs, across 32 genomes in Brassicaceae. Among these, 3347 genes were duplicated, with segmented duplication primarily contributing to their expansion. We identified 466 physical gene clusters, including 240 homogenous clusters and 226 heterogeneous clusters, shedding light on the organization of heat shock related genes. Notably, 37 genes were co-located with published thermotolerance quantitative trait loci, which supports their functional role in conferring heat stress tolerance. This study provides a comprehensive resource for the identification of functional Brassicaceae heat shock related genes, elucidates their clustering and duplication patterns and establishes the genomic foundation for future heat tolerance research. We hypothesise that genetic variants in HSP and HSF genes in certain species have potential for improving heat stress tolerance in Brassicaceae crops.

The mechanism and therapeutic strategies in doxorubicin-inducedcardiotoxicity: Role of programmed cell death.

Doxorubicin (DOX) is the most commonly used anthracycline anticancer agent, while its clinical utility is limited by harmful side effects like cardiotoxicity. Numerous studies have elucidated that programmed cell death plays a significant role in DOX-induced cardiotoxicity (DIC). This review summarizes several kinds of programmed cell death, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Furthermore, oxidative stress, inflammation, and mitochondrial dysfunction are also important factors in the molecular mechanisms of DIC. Besides, a comprehensive understanding of specific signal pathways of DIC can be helpful to its treatment. Therefore, the related signal pathways are elucidated in this review, including sirtuin deacetylase (silent information regulator 2 [Sir2]) 1 (SIRT1)/nuclear factor erythroid 2-related factor 2, SIRT1/Klotho, SIRT1/Recombinant Sestrin 2, adenosine monophosphate-activated protein kinase, AKT, and peroxisome proliferator-activated receptor. Heat shock proteins function as chaperones, which play an important role in various stressful situations, especially in the heart. Thus, some of heat shock proteins involved in DIC are also included. Hence, the last part of this review focuses on the therapeutic research based on the mechanisms above.

Targeting HSP90 in Gynecologic Cancer: Molecular Mechanisms and Therapeutic Approaches.

One of the leading causes of mortality for women is gynecologic cancer (GC). Numerous molecules (tumor suppressor genes or oncogenes) are involved in this form of cancer's invasion, metastasis, tumorigenic process, and therapy resistance. Currently, there is a shortage of efficient methods to eliminate these diseases, hence it is crucial to carry out more extensive studies on GCs. Novel pharmaceuticals are required to surmount this predicament. Highly conserved molecular chaperon, heat shock protein (HSP) 90, is essential for the maturation of recently produced polypeptides and offers a refuge for misfolding or denatured proteins to be turned around. In cancer, the client proteins of HSP90 play a role in the entire process of oncogenesis, which is linked to all the characteristic features of cancer. In this study, we explore the various functions of HSPs in GC progression. We also discuss their potential as promising targets for pharmacological therapy.

Genome-wide identification and coexpression network analysis of heat shock protein superfamily in Apolygus lucorum.

Heat shock proteins (Hsp) function as crucial molecular chaperones, playing pivotal roles in insects' response to stress stimuli. Apolygus lucorum, known for its broad spectrum of host plants and significant crop damage potential, presents a compelling subject for understanding stress response mechanisms. Hsp is important for A. lucorum to tolerate temperature and insecticide stress and may be involved in the formation of resistance to the interactive effects of temperature and insecticide. Here, we employed comprehensive genomic approaches to identify Hsp superfamily members in its genome. In total, we identified 42 Hsp genes, including 3 Hsp90, 16 Hsp70, 13 Hsp60, and 10 Hsp20. Notably, we conducted motif analysis and gene structures for Hsp members, which suggested the same families are relatively conserved. Furthermore, leveraging the weighted gene coexpression network analysis, we observed diverse expression patterns of different Hsp types across various tissues, with certain Hsp70 showing tissue-specific bias. Noteworthy among the highly expressed Hsp genes was testis-specific, which may serve as a pivotal hub gene regulating the gene network. Our findings shed light on the molecular evolutionary dynamics and temperature stress response mechanisms of Hsp genes in A. lucorum, offering insights into its adaptive strategies and potential targets for pest management.

Toxoplasma gondii bradyzoite-specific BAG1 is nonessential for cyst formation due to compensation by other heat-shock proteins

BackgroundToxoplasma gondii is an opportunistic pathogenic protozoan that infects all warm-blooded animals, including humans, and causes zoonotic toxoplasmosis. The bradyzoite antigen 1 (BAG1), known as heat-shock protein (HSP)30, is a specific antigen expressed during the early stage of T. gondii tachyzoite–bradyzoite conversion.MethodsA bag1 gene knockout strain based on the T. gondii type II ME49 was constructed and designated as ME49Δbag1. The invasion, proliferation, and cyst formation efficiency in the cell model and survival in the mouse model were compared between the ME49 and ME49Δbag1 strains after infection. Quantitative polymerase chain reaction (qPCR) was used to detect the transcriptional level of important genes, and western-blot was used to detect protein levels.ResultsME49Δbag1 displayed significantly inhibited cyst formation, although it was not completely blocked. During early differentiation induced by alkaline and starvation conditions in vitro, the proliferation of ME49Δbag1 was significantly accelerated relative to the ME49 strain. Meanwhile, the transcription of the HSP family and bradyzoite formation deficient 1 (bfd1) were significantly enhanced. The observed upregulation suggests a compensatory mechanism to counterbalance the impaired stress responses of T. gondii following bag1 knockout. On the other hand, the elevated transcription levels of several HSP family members, including HSP20, HSP21, HSP40, HSP60, HSP70, and HSP90, along with BFD1, implied the involvement of alternative regulatory factors in bradyzoite differentiation aside from BAG1.ConclusionsThe data suggested that when bag1 was absent, the stress response of T. gondii was partially compensated by increased levels of other HSPs, resulting in the formation of fewer cysts. This highlighted a complex regulatory network beyond BAG1 influencing the parasite’s transformation into bradyzoites, emphasizing the vital compensatory function of HSPs in the T. gondii life cycle adaptation.Graphical

Diminish the chances of Mediterranean fruit fly Ceratitis capitata eggs surviving by suppressing the expression of the heat shock protein 27 gene (Hsp27).

The hypothesized role of stress-inducible heat shock proteins is to act as a buffer against environmental variations and affect fitness in suboptimal conditions. Our study examining the functions of heat shock protein 27 (Hsp27) in the eggs of the Mediterranean fruit fly (Ceratitis capitata). We utilized double-stranded RNA, specifically targeting the Hsp27 gene, to reduce its expression and assessed the consequent impact on egg viability. The investigation included the examination of early eggs (less than 6 hours post-laying) and late eggs (more than 42 hours post-laying), using varying concentrations (0.02, 0.1, and 0.2 µg/µL) of Hsp27 dsRNA. Control groups of eggs were dsRNA of ATPase, Cctra-2, or phosphate buffer solution (ph-B-S). Down-regulating Hsp27 dsRNA reduced the hatching rate of the eggs compared to the hatching rate in the control groups, especially in the ph-B-S group. The early eggs were more affected than the late eggs after soaking with Hsp27 dsRNA, where the Hsp27 dsRNA decreased the hatching rates to 12.91% early. The tested concentration of 0.2 µg/µL of Hsp27 dsRNA was achieved with the most significant reduction of 2.75 in egg viability. The sex ratio of insects hatched from treated eggs was investigated after hatching. After the down-regulation of Hsp27, there was no significant effect of the Hsp27 down-regulation on the sex ratio.

Are Heat Shock Proteins Important in Low-Temperature-Stressed Plants? A Minireview

Heat shock proteins (HSPs) are mainly known to play important roles in plants against high-temperature (HT) stress. Their main function is to act as molecular chaperones for other proteins. It has also been proven that HSPs have a protective effect during other environmental stresses including low temperature (LT). To the best of our knowledge, the expression and role of HSPs in plants that have been exposed to LT have not yet been sufficiently reviewed. The aims of this minireview were (1) to briefly describe the origin, classification, structure, localisation and functions of HSPs, (2) to present the current knowledge about the changes in the accumulation of HSPs in plants that have been exposed to LT, (3) to discuss some of the molecular changes that occur during LT action and that lead to the accumulation of HSPs in plants and (4) to discuss the potential role of HSPs in acquiring tolerance to cold and frost in plants including economically important crop species. Some directions of research on the role of HSPs in plants growing in LT conditions are proposed.

The analysis of inducible family members in the water flea Daphnia magna led to the identification of an uncharacterized lineage of heat shock protein 70

To explore the function and evolutionary relationships of inducible heat shock protein 70 (Hsp70) in Daphnia magna, cDNAs of four Hsp70 family members (DmaHsp70, DmaHsp70-2, DmaHsp70-12, DmaHsp70-14) were cloned. While all DmaHsp70s possess three function domains, it is noteworthy that only DmaHsp70 ends with a “EEVD” motif. Phylogenetic analysis indicates that the Hsp70-12 lineage is distanced from the rest, and therefore it is an uncharacterized lineage of Hsp70. The differences in isoelectric point and 3-dimensional (3D) conformation of the N-terminal nucleotide binding domain (NBD) of DmaHsp70s further support the theory. DmaHsp70s exhibit varied motif distribution patterns and the logo sequences of motifs have diverse signature characteristics, indicating that different mechanisms are involved in the regulation of ATP binding and hydrolysis for the DmaHsp70s. Protein-protein network together with the predicted subcellular locations of DmaHsp70s suggest that they likely fulfill distinct roles in cells. The transcription of four DmaHsp70s were changed during the recovery stage after thermal stress or oxidative stress. But the expression pattern of them were dissimilar. Collectively, these results collectively elucidated the identification of a previously uncharacterizedHsp70 lineage in animal and extended our understanding of the Hsp70 family.

Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.

The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases.

Hsp90-Mediated Multi-Drug Resistance in DNA Polymerase-Defective Strains of Candida albicans.

The incidence of infections caused by Candida species, specifically by drug-resistant isolates, is a major health concern as they can disseminate to and colonize most vital organs, enhancing morbidity and mortality. Several molecular mechanisms have been reported to be involved in drug resistance. These are mostly drug- and isolate-specific. Here, we characterized three different genetically modified strains of C. albicans that were multi-drug-resistant (MDR) and deciphered a uniform mechanism responsible for resistance. DNA polymerase epsilon (Polε) is a leading strand-specific polymerase consisting of four subunits, namely, Pol2, Dpb2, Dpb3, and Dpb4. The deletion of one or both of the Dpb3 and Dpb4 subunits in C. albicans rendered multi-drug resistance. A detailed characterization of these strains revealed that acquired mutagenesis, drug efflux pumps, and other known mechanisms did not play a significant role because the complemented strain showed drug sensitivity. More importantly, the function of heat shock protein 90 (Hsp90) in these knockout strains is critical for reducing susceptibility to several antifungal drugs. Cell wall deformity and composition in these strains can add to such a phenotype. The inhibition of Hsp90 function by geldanamycin and tricostatin A sensitized the MDR strains to antifungals. Considering our earlier research and this report, we suggest that replication stress induces Hsp90 expression and activity in order to orchestrate a cellular stress response circuit and thus develop fungal drug resistance. Thus, Hsp90 is an important drug target for use in combinatorial therapy.

Escherichia coli-based Complementation Assay to Study the Chaperone Function of Heat Shock Protein 70.

Heat shock protein 70 (Hsp70) is a conserved protein that facilitates the folding of other proteins within the cell, making it a molecular chaperone. While Hsp70 is not essential for E. coli cells growing under normal conditions, this chaperone becomes indispensable for growth at elevated temperatures. Since Hsp70 is highly conserved, one way to study the chaperone function of Hsp70genes from various species is to heterologously express them in E. coli strains that are either deficient in Hsp70 or express a native Hsp70 that is functionally compromised. E. coli dnaK756cells are unable to support λ bacteriophage DNA. Furthermore, their native Hsp70 (DnaK) exhibits elevated ATPase activity while demonstrating reduced affinity for GrpE (Hsp70 nucleotide exchange factor). As a result, E. coli dnaK756cells grow adequately at temperatures ranging from 30 °C to 37 °C, but they die at elevated temperatures (>40 °C). For this reason, these cells serve as a model for studying the chaperone activity of Hsp70. Here, we describe a detailed protocol for the application of these cells to conduct a complementation assay, enabling the study of the in cellulo chaperone function of Hsp70.

Heat shock protein paradigms in cancer progression: future therapeutic perspectives.

Heat-shock proteins (HSPs), also known as stress proteins, are ubiquitously present in all forms of life. They play pivotal roles in protein folding and unfolding, the formation of multiprotein complexes, the transportation and sorting of proteins into their designated subcellular compartments, the regulation of the cell cycle, and signalling processes. These HSPs encompass HSP27, HSP40, HSP70, HSP60, and HSP90, each contributing to various cellular functions. In the context of cancer, HSPs exert influence by either inhibiting or activating diverse signalling pathways, thereby impacting growth, differentiation, and cell division. This article offers an extensive exploration of the functions of HSPs within the realms of pharmacology and cancer biology. HSPs are believed to play substantial roles in the mechanisms underlying the initiation and progression of cancer. They hold promise as valuable clinical markers for cancer diagnosis, potential targets for therapeutic interventions, and indicators of disease progression. In times of cellular stress, HSPs function as molecular chaperones, safeguarding the structural and functional integrity of proteins and aiding in their proper folding. Moreover, HSPs play a crucial role in cancer growth, by regulating processes such as angiogenesis, cell proliferation, migration, invasion, and metastasis.

Roles of heat shock proteins in tumor immune microenvironment

Heat shock proteins (HSPs) are the most abundant molecular chaperones in cells, categorized based on function and molecular weight into HSP families, namely, HSP40, HSP70, HSP90, HSP110, and HSPB (heat shock protein B), et al. HSPs are involved in protein homeostasis by assisting in the correct folding of proteins or incorrectly folded proteins, refolding partially denatured proteins, and degrading damaged proteins. High levels of HSPs have been shown to participate in oncogenesis, progression, and chemotherapy resistance in many cancers. Recently a new range of functions besides chaperons, mostly in modulation of immune responses, have been shown for these extracellular HSPs. Here, we review the interactions between the HSPs and different immune cells, such as T lymphocytes, B cells, dendritic cells, macrophages, NK cells, and myeloid suppressor cells in the tumor microenvironment, as well as tumor vasculature and angiogenesis in tumor formation. The underlying mechanisms of HSPs’ regulation on immune response in tumor microenvironments are also discussed. The understanding of new functions of HSPs in tumor microenvironment may provide critical insights for the development of effective immunotherapies.

Genome-wide identification of heat shock protein gene family and their responses to pathogen challenge in Trachinotus ovatus

Heat Shock Proteins (HSPs) are a widely distributed family of proteins produced in response to heat and other stresses. To develop a deeper understanding of the mechanisms governing expression of HSPs in the bony fish Trachinotus ovatus, we carried out a whole genome analysis and identified 43 HSP genes. Based on their phylogenetic relationships with Danio rerio, Seriola dumerili, and Seriola lalandi, they were divided into four subfamilies: HSP20, HSP60, HSP70, and HSP90. We performed an analysis of the predicted physicochemical properties and subcellular localization of proteins encoded by these genes. The chromosomal localization results showed that the HSP genes are distributed across 20 chromosomes of T. ovatus.These genes were found to be expressed in different tissues, and they showed differential expression in the immune response against Streptococcus agalactiae. However, there was no significant differential expression in the different skin tissue locations of T. ovatus after infection by Cryptocaryon irritans Brown. This study provides basic information for further research on the evolution and structure and function of HSPs in teleosts.

The proteomics analysis of extracellular vesicles revealed the possible function of heat shock protein 60 in Helicobacter pylori infection

BackgroundHelicobacter pylori (H. pylori) infection is a major risk factor for gastric diseases, including gastritis and gastric cancer. Heat shock protein 60 (HSP60) is a chaperone protein involved in various cellular processes and has been implicated in the immune response to bacterial infections. Extracellular vesicles (EVs) containing various protein components play important roles in cell communication. In the present study, a systematic proteomic analysis of EVs obtained from H. pylori infected cells was performed and the EV-derived HSP60 function was studied.MethodsEVs were evaluated by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The recognized protein components were quantified by label-free proteomics and subjected to bioinformatics assays. The expression of HSP60 in EVs, host cells and gastric cancers infected by H. pylori was determined by western blotting and immunohistochemical, respectively. In addition, the apoptotic regulation mechanisms of HSP60 in H. pylori infection were analyzed by western blotting and flow cytometry.ResultsA total of 120 important differential proteins were identified in the EVs from H. pylori-infected cells and subjected to Gene Ontology analysis. Among them, CD63, HSP-70 and TSG101 were verified via western blotting. Moreover, HSP60 expression was significantly increased in the EVs from H. pylori-infected GES-1 cells. H. pylori infection promoted an abnormal increase in HSP60 expression in GES-1 cells, AGS cells, gastric mucosa and gastric cancer. In addition, knockdown of HSP60 suppressed the apoptosis of infected cells and the expression of Bcl2, and promoted the upregulation of Bax.ConclusionThis study provides a comprehensive proteomic profile of EVs from H. pylori-infected cells, shedding light on the potential role of HSP60 in H. pylori infection. The findings underscore the significance of EV-derived HSP60 in the pathophysiology of H. pylori-associated diseases.

Hsp70 and Hsp90 Elaborately Regulate RNAi Efficiency in Plutella xylostella.

Heat-shock proteins (HSPs) serve as molecular chaperones in the RNA interference (RNAi) pathway of eukaryotic organisms. In model organisms, Hsp70 and Hsp90 facilitate the folding and remodeling of the client protein Argonaute (Ago). However, the specific function of HSPs in the RNAi pathway of Plutella xylostella (L.) (Lepidoptera: Plutellidae) remains unknown. In this study, we identified and analyzed the coding sequences of PxHsc70-4 and PxHsp83 (also known as PxHsp90). Both PxHsc70-4 and PxHsp83 exhibited three conserved domains that covered a massive portion of their respective regions. The knockdown or inhibition of PxHsc70-4 and PxHsp83 in vitro resulted in a significant increase in the gene expression of the dsRNA-silenced reporter gene PxmRPS18, leading to a decrease in its RNAi efficiency. Interestingly, the overexpression of PxHsc70-4 and PxHsp83 in DBM, Sf9, and S2 cells resulted in an increase in the bioluminescent activity of dsRNA-silenced luciferase, indicating a decrease in its RNAi efficiency via the overexpression of Hsp70/Hsp90. Furthermore, the inhibition of PxHsc70-4 and PxHsp83 in vivo resulted in a significant increase in the gene expression of PxmRPS18. These findings demonstrated the essential involvement of a specific quantity of Hsc70-4 and Hsp83 in the siRNA pathway in P. xylostella. Our study offers novel insights into the roles played by HSPs in the siRNA pathway in lepidopteran insects.

Heat Shock Proteins’ Expression Profiles in Odontogenic Ameloblastomas and Cysts

Tumors and cysts with odontogenic origin represent a family of lesions with specific histo-genetic and clinical characteristics. Among them, ameloblastomas are common benign neoplasms, predominantly detected in the anatomic areas of the jaws and also in the mandible and maxilla. Although they are characterized by a slow and stable growing pattern, a subset of them shows a tendency for local tissue invasiveness and partially increased recurrence rates after surgical excision. Furthermore, heat shock proteins (HSPs) are potentially implicated in ameloblastoma onset and progression. HSPs regulate the folding and refolding of proteins and are induced in response to oxidative stress. They are crucial members of the chaperone intracellular system and are categorized based on their molecular weight (i.e., HSP27, HSP60, HSP70, HSP90). In the current review, we describe HSPs origin and function, focusing on their deregulation mechanisms and impact predominantly on ameloblastomas and also on inflammatory and developmental odontogenic cystic lesions.

Spatiotemporal Patterns of Five Small Heat Shock Protein Genes in Hyphantria cunea in Response to Thermal Stress.

Hyphantria cunea (Drury), a destructive polyphagous pest, has been spreading southward after invading northern China, which indicates that this insect species is facing a huge thermal challenge. Small heat shock proteins (sHSPs) function as ATP-independent molecular chaperones that protect insects from heat stress damage. In order to explore the role of sHSPs in the thermotolerance of H. cunea, five novel sHSP genes of H. cunea were cloned, including an orthologous gene (HcHSP21.4) and four species-specific sHSP genes (HcHSP18.9, HcHSP20.1, HcHSP21.5, and HcHSP29.8). Bioinformatics analysis showed that the proteins encoded by these five HcHSPs contained typical α-crystallin domains. Quantitative real-time PCR analysis revealed the ubiquitous expression of all HcHSPs across all developmental stages of H. cunea, with the highest expression levels in pupae and adults. Four species-specific HcHSPs were sensitive to high temperatures. The expression levels of HcHSPs were significantly up-regulated under heat stress and increased with increasing temperature. The expression levels of HcHSPs in eggs exhibited an initial up-regulation in response to a temperature of 40 °C. In other developmental stages, the transcription of HcHSPs was immediately up-regulated at 30 °C or 35 °C. HcHSPs transcripts were abundant in the cuticle before and after heat shock. The expression of HcHSP21.4 showed weak responses to heat stress and constitutive expression in the tissues tested. These results suggest that most of the HcHSPs are involved in high-temperature response and may also have functions in the normal development and reproduction of H. cunea.

Crossroad between the Heat Shock Protein and Inflammation Pathway in Acquiring Drug Resistance: A Possible Target for Future Cancer Therapeutics.

The development of multidrug resistance (MDR) against chemotherapeutic agents has become a major impediment in cancer therapy. Understanding the underlying mechanism behind MDR can guide future treatment for cancer with better therapeutic outcomes. Recent studies evidenced that crossroads interaction between the heat shock proteins (HSP) and inflammatory responses under the tumor microenvironment plays a pivotal role in modulating drug responsiveness and drug resistance through a complex cytological process. This review aims to investigate the interrelationship between inflammation and HSP in acquiring multiple drug resistance and investigate strategies to overcome the drug resistance to improve the efficacy of cancer treatment. HSP plays a dual regulatory effect as an immunosuppressive and immunostimulatory agent, involving the simultaneous blockade of multiple signaling pathways in acquiring MDR. For example, HSP27 shows biological effects on monocytes by causing IL10 and TNFα secretion and blocking monocyte differentiation to normal dendritic cells and tumor-associated macrophages to promote cancer progression and chemoresistance. Thus, the HSP function and immune-checkpoint release modalities provide a therapeutic target for a therapeutically beneficial approach for enhancing anti-tumor immune responses. The interconnection between inflammation and HSP, along with the tumor microenvironment in acquiring drug resistance, has become crucial for rationalizing the effect of HSP immunomodulatory activity with immune checkpoint blockade. This relationship can overcome drug resistance and assist in the development of novel combinatorial cancer immunotherapy in fighting cancer with decreasing mortality rates.